TABLE OF CONTENTS
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We are a global biotechnology company dedicated to making a major impact on the lives of people with serious diseases. Our broad product and service portfolio is focused on rare disorders, renal diseases, orthopaedics, organ transplant, and diagnostic and predictive testing.testing, and cancer. We were formed as a Delaware corporation in June 1981 and became a Massachusetts corporation in 1991. We are organized into fivesix financial reporting units, which we also consider to be our reporting segments:
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- Renal, which develops, manufactures and distributes products that treat patients suffering from renal diseases, including chronic renal failure. The unit derives substantially all of its revenue from sales of Renagel (including sales of bulk sevelamer) and Hectorol;
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- Therapeutics, which develops, manufactures and distributes therapeutic products, with an expanding focus on products to treat patients suffering from genetic diseases and other chronic debilitating diseases, including a family of diseases known as lysosomal storage disorders, or LSDs, and other specialty therapeutics, such as Thyrogen. The unit derives substantially all of its revenue from sales of Cerezyme, Fabrazyme, Myozyme and Thyrogen;
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- Transplant, which develops, manufactures and distributes therapeutic products that address
thepre-transplantation, prevention and treatment ofacutegraft rejection in organ transplantationas well asand other hematologic and auto-immune disorders. The unit derives substantially all of its revenue from sales ofThymoglobulin and Lymphoglobuline;·Thymoglobulin; - •
- Biosurgery, which develops, manufactures and distributes biotherapeutics and biomaterial-based products, with an emphasis on products that meet medical needs in the orthopaedics and broader surgical areas. The unit derives substantially all of its revenue from sales of Synvisc, the Sepra line of products, Carticel and Matrix-induced Autologous Chondrocyte Implantation, or MACI;
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- Genetics, which provides testing services for the oncology, prenatal and reproductive
markets.markets; and - •
- Oncology, which develops, manufactures and distributes products for the treatment of cancer, with a focus on antibody- and small molecule-based therapies. The unit derives substantially all of its revenue from sales and royalties received on sales of Campath and Clolar and from the reimbursement of Campath development expenses.
We report the activities of our diagnostic products, oncology, bulk pharmaceuticals and cardiovascular business units under the caption “Other.”"Other." We report our corporate, general and administrative operations and corporate science activities under the caption “Corporate.”"Corporate."
Renal
Renagel (sevelamer hydrochloride)/ Renvela (sevelamer carbonate).Renagel is a non-absorbed, calcium-free, metal-free phosphate binder indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on hemodialysis. In October 2007, our label was expanded for use in CKD patients on dialysis, which includes both hemodialysis and peritoneal dialysis. Three formulations of the product have been approved for sale in the U.S.—United States—the 403 mg. capsules were launched in the fourth quarter of 1998, and the 400 and 800 mg. tablets were launched in September 2000. We ceased marketing the 403 mg. capsules in 2004. Renagel was approved for sale in Israel in 1999, the European Union and Canada in 2000, Brazil in 2002, Japan in 2003, Argentina and
Australia in 2005, and Chile and Peru in 2006.2006, and Mexico in 2007. In the U.S.,United States, there are an estimated 371,000374,000 end-stage renal disease patients, approximately 95%90% of whom receive a phosphate control product. There are also an estimated 324,000 end-stage renal disease patients in Europe, 65,000 in Brazil, 30,00019,700 in Canada and 238,000258,000 in Japan. We are now marketing the product in over 50 countries.
We market Renagel tablets in the U.S., the European UnionUnited States, Europe, Canada, Latin America and BrazilAustralia directly to nephrologists through a dedicated sales force. In the U.S.,United States, approximately 85%–—90% of our Renagel sales are made to three large wholesalers. These wholesalers distribute Renagel to retail pharmacies, hospitals and other providers of medication to patients. Chugai Pharmaceutical Co., Ltd. and its partner, Kirin Brewery Co., Ltd., have rights to develop and market Renagel in Japan, China and other Pacific Rim countries. Our
sales of Renagel (including sales of bulk sevelamer), totaled $602.7 million, or 16% of our total revenue in 2007, $515.1 million, or 18%16% of our consolidated product revenuestotal revenue in 2006, and $417.5 million, or 17%15% of our consolidated product revenuestotal revenue in 2005, and $363.7 million, or 18% of our consolidated product revenues in 2004.2005.
We conducted the largest prospective dialysis outcomes study, a 2,100-patient post-marketing study of Renagel to evaluate the ability of the product to improve patient morbidity and mortality. The Dialysis Clinical Outcomes Revisited, or DCOR, trial compared Renagel to calcium-based phosphate binders with respect to overall morbidity and mortality. We presented the data from this trial at the American Society of Nephrology (ASN) meeting in November 2005. The study did not meet its primary end point of a statistically significant reduction in all cause mortality. However, in a pre-specified sub-group analysis, Renagel demonstrated a significant reduction in all cause mortality in patients 65 years of age or older. The DCOR study included morbidity data from the Centers for Medicare and Medicaid Services (CMS), which were presented at the 2006 ASN meeting. This data showed patients receiving Renagel experienced lower rates of hospitalization, fewer days in the hospital, and reduced overall health care expenditures compared to patients treated with calcium-based phosphate binders. In early 2007,Kidney Internationalpublished findings from the Renagel in New Dialysis, or RIND, study that showdemonstrated a significantly lower rate of death among patients treated with Renagel from the time they began dialysis compared with those using calcium-based phosphate binders. Also published inKidney Internationalin August 2007, were the results of the Dialysis Clinical Outcomes Revisited study, or DCOR, a three-year trial involving more than 2,100 patients on hemodialysis. DCOR was conducted to compare the difference in outcomes for patients receiving Renagel with those using calcium-based phosphate binders. This is the largest prospective dialysis outcomes study conducted to evaluate the ability of Renagel to improve patient mortality and morbidity. While the study did not meet its primary endpoint of a statistically significant reduction in all cause mortality, in a pre-specified secondary analysis, Renagel demonstrated a significant reduction in all cause mortality in patients 65 years of age or older. Additionally, the mean number of hospitalizations and hospital days were lower in the Renagel-treated arm. For patients remaining on study for at least two years, a difference in mortality emerged favoring the Renagel patients. These studies, in combination with previously completed studies, provide a significant body of evidence helping to demonstrate the effectiveness of Renagel.
On December 21, 2006, we filed a New Drug Application (NDA) with In the fourth quarter of 2007, the FDA seekinggranted marketing approval of sevelamer carbonatefor Renvela tablets for the control of serum phosphorus in patients with CKD on dialysis, including both hemodialysis and peritoneal dialysis. If approved, we expect sevelamerRenvela is a next-generation version of Renagel and will initially be available as 800 mg tablets. Renvela offers all of the advantages of Renagel with the added benefit of a carbonate will be marketed under the trade name RenvelaTM.buffer. In addition, we are advancing a clinical program investigatingstudy comparing Renvela to Renagel in patients on hemodialysis, both drugs demonstrated equivalent control of serum phosphorus to within Kidney Disease Outcomes Quality Initiative, or KDOQI, recommended ranges. Patients on Renvela, however, were more likely to maintain bicarbonate levels within the userecommended KDOQI ranges, and had a lower incidence of gastrointestinal adverse events. We plan to pursue regulatory approvals for Renvela in Europe, Latin America and in other markets internationally. While Renagel will remain available for hyperphosphatemica period of time, our long-term goal is to transition patients with CKD who have not progressed to dialysis. Enrollment isRenvela.
We also complete incompleted a study comparing a powder form of sevelamer carbonateRenvela dosed once athree times per day to Renagel tablets dosed three times a day.per day in patients on hemodialysis. This study met its primary endpoint of achieving equivalent phosphorus control in patients treated with both Renvela and Renagel. We believe developmentexpect to file for approval of the powder form of Renvela, which may represent a promising alternative for patients with CKD by making it easier for patients to comply with their prescribed treatment program, in the product would offerfirst half of 2008.
In the third quarter of 2007, we participated in the FDA's Cardiovascular and Renal Products Advisory Committee meeting. During this meeting, the committee recommended that the FDA extend the indications for phosphate binder use in pre-dialysis patients with hyperphosphatemia. We have successfully completed a more convenient optionstudy with Renvela in CKD patients not on dialysis, and we plan to patients, thereby improving compliance.continue
to work with the FDA on the appropriate regulatory path forward to achieve approval of Renvela for this patient population.
Hectorol (doxercalciferol).We added Hectorol to our product portfolio in July 2005 through our acquisition of Bone Care International, Inc., or Bone Care. Hectorol is a line of vitamin D2 pro-hormone products that are indicated for the treatment of secondary hyperparathyroidism in patients with stages 3 and 4 CKD (0.5 mcg and 2.5 mcg capsules) and in patients with stage 5 CKD on dialysis (2.5 mcg capsules and injection). Hectorol provides significant parathyroid hormone (PTH) reductions with minimal impact on calcium and phosphorus levels. Three formulations of the product have been approved for commercial sale in the U.S.—United States—the 2.5 mcg capsules were approved in 1999, the 0.5 mcg capsules were approved in 2004 and the intravenous formulation was approved in 2000. TheWe received approval on Hectorol 2.5 mcg formulation also is approvedand 0.5 mcg capsules in Canada, where it is marketedArgentina in 2007 and sold by Shire BioChem, a Canadian subsidiary of Shire plc, or Shire.expect to launch in that country in early 2008.
We market Hectorol in the U.S.United States through a direct sales force focused on nephrologists. Approximately 85%–—90% of our U.S. Hectorol capsule sales are made to three large wholesalers, who then sell and distribute the product to retail pharmacies, hospitals and other providers of medication to patients. For Hectorol IV, approximately 85%–—90% of our sales are made to three primary wholesalers who then sell and distribute the product to dialysis chains and hospitals. In the U.S.,United States, approximately 65% of end-stage renal disease patients receive Vitamin D. We estimate that there are more than 2.5 million patients in the U.S.United States with stage 3 and stage 4 CKD who have elevated PTH levels, although only a much smaller number of patients are being treated for the condition. In December 2006, Dr. Francesca Tentoriet al published data inKidney International distinguishing vitaminVitamin D analogs. These findings suggest that treatment with vitaminVitamin D analogs provides a significant advantage for dialysis patients and that the newer generation of D2 analogs, such as Hectorol, appear to have survival advantages over older analogs such as calcitriol.
In 2007, Genzyme filed an IND for the use of Hectorol in psoriasis patients. We plan to initiate a clinical trial in this indication in early 2008.
Therapeutics
Our Therapeutics segment currently has fivesix therapeutic products on the market and several other therapeutic products in varying stages of development. The chart set forth below provides summary information on five of these five products one of which we sell on behalf of a joint venture, as of February 28, 2007.1, 2008.
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Cerezyme/Ceredase | Type 1 Gaucher disease; Type 3 Gaucher disease (Cerezyme/European Union only) | Ceredase sold commercially since 1991; Cerezyme marketed since 1994; marketing approval received and commercial sales in | |||||||||||||
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Cerezyme, Fabrazyme, Myozyme and Aldurazyme are each aimed at treating LSDs with patient populations of less than 10,000 worldwide. Additional details on our Therapeutic products are set forth below.
Cerezyme (imiglucerase).We are marketing Cerezyme as an enzyme replacement therapy for the treatment of Gaucher disease, an LSD that is caused by a deficiency in the enzyme glucocerebrosidase, which causes fatty deposits to build up in certain organs and bones leading to a wide variety of symptoms, including anemia, spleen and liver enlargement and bone deterioration. Treatment with Cerezyme enzyme replacement therapy currently represents the only safe and effective enzyme replacement therapy approved for treatment of Type 1 Gaucher disease. In the EEuropean Union,uropean Union,
Cerezyme is also approved for the
treatment of patients who exhibit clinically significant, non-neurological manifestations of the disease (Type 3 Gaucher disease).
We market Cerezyme directly to physicians, hospitals and treatment centers worldwide through a highly specialized sales force. Our results of operations are highly dependent on sales of this product, although our dependence is lessening as we diversify our product portfolio. Sales of Cerezyme totaled $1.1 billion, or 30% of our total revenue in 2007, $1.0 billion, or 35%32% of our consolidated product revenuestotal revenue in 2006, and $932.3 million, or 38%34% of our consolidated product revenuestotal revenue in 2005, and $839.4 million, or 42% of our consolidated product revenues in 2004.2005.
Fabrazyme (agalsidase beta).We have developed Fabrazyme, a recombinant form of the human enzyme alpha-galactosidase, as a treatment for Fabry disease. Fabry disease is an LSD that is caused by a deficiency of the enzyme alpha-galactosidase A, which leads to the progressive accumulation of lipids within cells of the kidneys, heart and other organs. In agreement with the FDA and EMEA, we undertook a number of post-marketing commitments, and have completed a phase 4, multi-national, multi-center, double-blind placebo-controlled study. In January 2007, the results of this trial were published in the Annals of Internal Medicine. In mid-2005, theThe EMEA approved new labeling for Fabrazyme based largely on the results from the phase 4 study.study in mid-2005. In January 2007, the results of this trial were published in theAnnals of Internal Medicine. In May 2007, the data from the phase 3 extension trial were also published. This data showed that Fabrazyme stabilizes renal function in Fabry patients over a 54 month period. In early 2008, the EMEA granted full marketing authorization for Fabrazyme, making it the only product on the market for Fabry disease to earn this designation in the European Union. Because kidney failure is associated with Fabry disease, Fabrazyme is sold by our existing LSD and Renal sales forces.
Thyrogen (thyrotropin alfa).Thyrogen is an adjunctive diagnostic agent used in the follow-up of patients with well-differentiated thyroid cancer. We developed this product to allow patients to continue taking their thyroid hormone supplements while they are being screened for residual or recurring thyroid cancer. This helps patients avoid the debilitating effects of hypothyroidism, increasing the likelihood that they will seek follow-up treatment, and ultimately improve the likelihood of early detection of any recurrent disease, which can improve the success rate of subsequent treatment. In the U.S.United States and the European Union, physicians order over 200,000 thyroid cancer screening tests per year. Thyrogen is promoted by a dedicated sales force, and sold to hospitals and doctors’ offices through distributors in the U.S., Brazil and the European Union.
We currently are pursuing additional indications for Thyrogen. In March 2005,December 2007, we received European UnionFDA approval to market Thyrogen as an adjunctive treatment for ablation or destruction of thyroid remnants in patients who have undergone removal of their thyroid for the treatment of well-differentiated thyroid cancer. This indication compliments the diagnostic use of Thyrogen in combination with radioiodine in ablationthat it enables use for an additional stage of thyroid tissue. We received an approvable letter for this indicationcancer management. As in its diagnostic use, Thyrogen allows patients to remain on thyroid hormone therapy while undergoing radioiodine ablation, thus helping prevent the debilitating effects of hypothyroidism. Another advantage to Thyrogen use is that the patients taking it clear radioiodine more rapidly from the FDA in August 2005 and completed a clinical study to fulfill one of the requirements in the approvable letter in the fourth quarter 2006. We expect to file the amended supplemental New Drug Application (NDA) in 2007 and anticipate approval in the U.S., Brazil and Canada in 2008.their system than do patients receiving thyroid hormone withdrawal. Approximately 35,000 ablation procedures are performed annually in the U.S.United States and European Union combined, and we believe that Thyrogen has the potential to be used in up to 80% of these procedures.
Thyrogen is promoted by a dedicated sales force, and sold to hospitals and doctors' offices through distributors in the United States, the European Union, Latin America and Asia. We also plan to begin a phase 2 trialcurrently are pursuing additional market or expanded indication approvals for Thyrogen and anticipate approvals in 2007 of TSH, the active ingredient in Thyrogen, for use in patients with nontoxic multinodular goiter.Japan, Canada, Colombia, Peru, Uruguay, South Korea, Singapore, Taiwan and Thailand.
Myozyme (alglucosidase alfa).We are marketing Myozyme as a therapy for Pompe disease, a progressive and often fatal muscle disease resulting from an inherited enzyme deficiency. Pompe disease manifests as a broad spectrum of clinical symptoms, with variable rates of progression ranging from rapidly progressive and often fatal within the first year of life from severe cardiac and skeletal muscle involvement to relentlessly progressive resulting in significant morbidity and premature mortality from skeletal and respiratory muscle involvement.mortality. Myozyme is the first and only treatment approved for Pompe disease and is indicated for all patients with the disorder. Myozyme specifically targets the underlying cause of Pompe disease by replacing the enzyme that is absent or deficient.
A randomized, double blind, placebo controlled, multi-center, multi-national clinical trial on juvenile and adult patients was completed in late 2007 and met both of its co-primary efficacy endpoints. The co-primary endpoints were functional endurance as measured by the 6 minute walk and pulmonary function as measured by percent predicted forced vital capacity. We are currently conducting a clinical trialcompleting the full analysis of late onset patientsthe study results and expectplan to havesubmit in the United States and European Union in the second half of 2008 for potential inclusion of the results in late 2007.the Myozyme product labeling.
Aldurazyme (laronidase).We In 1998, we formed a joint venture with BioMarin Pharmaceutical Inc., or BioMarin, and BioMarin Genetics, Inc. to develop and market Aldurazyme, a recombinant form of the human enzyme alpha-L-iduronidase, to treat an LSD known as mucopolysaccharidosis I, or MPS I. MPS I is a progressive, debilitating, and often life-threatening disease, which encompasses a wide and continuous
spectrum of clinical presentations, historically classified as “Hurler,” “Hurler-Scheie”"Hurler," "Hurler-Scheie" and “Scheie”"Scheie" syndromes. In 2003, Aldurazyme received marketing approval in both the United States and the European Union. We market Aldurazyme directly to physicians in the U.S.United States through our LSD sales force. In Europe, Latin America and Asia, sales of Aldurazyme are undertaken by the local sales and marketing teams and are being realized on a country-by-country basis as pricing and reimbursement approvals are obtained. The joint venture’s applicationsApplications for Aldurazyme marketing approval are currently pending in several countries in Latin America, Central and Eastern Europe, and the Asia-Pacific rim. We also completed a post-marketing clinical study investigating alternative dosing regimens in 2006.Through 2007, Aldurazyme revenues arewere recorded by the joint venture. We includeincluded our portion of the net income (loss) of BioMarin/Genzyme LLC in equity in income (loss) of equity method investments in our consolidated statements of operations.
Effective January 1, 2008, we restructured the relationship regarding the manufacturing and commercialization of Aldurazyme by entering into several new agreements. BioMarin/Genzyme LLC will no longer engage in commercial activities related to Aldurazyme and will solely hold the intellectual property relating to Aldurazyme and other collaboration products and engage in research and development activities that are mutually selected and funded by BioMarin and us, the costs of which will be shared equally.
Under the restructured relationship, BioMarin/Genzyme LLC will license all intellectual property relating to Aldurazyme and other collaboration products on a royalty-free basis to BioMarin and us. BioMarin will hold the manufacturing rights and we will hold the global marketing rights and we will pay BioMarin a tiered payment ranging from 39.5% to 50% of worldwide net product sales of Aldurazyme.
Transplant
This business segment includes three marketed products, as well as product candidates in the research and development stages that we acquired through our acquisition of SangStat Medical Corporation, or SangStat, in the third quarter of 2003 and our acquisition of AnorMED in the fourth quarter of 2006. Set forth below is a discussion of the two marketed productsproduct that areis the primary revenue driversdriver for the Transplant segment.
Thymoglobulin (anti-thymocyte globulin, rabbit). Thymoglobulin is an immunosuppressive polyclonal antibody that suppresses certain types of immune cells responsible for acute organ rejection in transplant patients. Thymoglobulin was approved in the U.S.United States in December 1998, and we market Thymoglobulin in the U.S.United States for the treatment of acute rejection of renal transplants. In Canada, we have marketed Thymoglobulin since 2003 for both the prevention and treatment of acute rejection of renal transplants. More kidney transplants are performed in the U.S.United States than any other organ transplant, with over 17,000 transplants performed in 2006. Of this number of renal transplants, the United Network for Organ Sharing estimates that acute immunosuppressant therapies such as Thymoglobulin were used in greater than 70% of such procedures.
In the European Union, Thymoglobulin has a broader approved label which allows us to market it for a wider variety of approved uses, including the prevention and treatment of rejection in solid organ transplants, the prevention and treatment of graft versus host disease, and the treatment of aplastic anemia, a disease that affects the production of mature, functional blood cells. Thymoglobulin also has a similarly broad label in several Asian and Latin American countries. WeThymoglobulin was launched in Mexico and we have filed for marketing approval of Thymoglobulin in Japan, Costa Rica, Australia, New Zealand and the UK.United Kingdom. We sell Thymoglobulin in 4751 countries through a direct sales force or through distributors to transplant centers for use by transplant surgeons, nephrologists, hematologists and oncologists.
We completed enrollment inare completing the one year follow-up of a phase 2 trial of Thymoglobulin in liver transplantation to prevent rejection and delay of the introduction of calcineurin inhibitors in patients with renal dysfunction prior to liver transplant. In collaboration with the Immune Tolerance Network, we have initiated a phase 2 trial to evaluate the effects of Thymoglobulin on preserving beta-cell function in patients with new onset Type 1 diabetes mellitus. We plan to conducthave initiated phase 2 clinical trials beginning in 2007 in North America and Europe forevaluating the use of Thymoglobulin in the treatment of immune mediated bone marrow failure associated with myelodysplastic syndromes.
Lymphoglobuline (anti-thymocyte-globuline, equine). We market Lymphoglobuline, another immunosuppressive polyclonal antibody, in Latin America, the European Union, and certain Asia Pacific countries for the treatment of aplastic anemia and for the prevention and treatment of graft rejection. This product is sold through our sales force in Europe and through distributors elsewhere.
Biosurgery
Synvisc (hylan G-F 20). Synvisc is a biomaterialbiomaterial-based product derived from hyaluronan used to treat the pain associated with osteoarthritis of the knee. An estimated 8 to 9 million of the approximately 14 million people in the U.S.United States with osteoarthritis of the knee may be candidates for treatment with Synvisc. Synvisc is sold commercially in over 60 countries, both directly and through marketing and distribution arrangements.
We arehave been investing in research and clinical trials to expand the use of Synvisc to additional joints and through next-generation approaches. In the European Union and Canada, Synvisc is approved for the treatment of pain associated with osteoarthritis of the hip, and in the European Union, we launched Synvisc is approved for the treatment of pain associated with osteoarthritis of the hip, ankle and shoulder in December 2006.shoulder.
In December 20062007 we completed a pivotal trial evaluatingreceived approval to market Synvisc-One, a single-injection regimen of Synvisc. We anticipate filing for approval of single-injection Synvisc, in the European UnionUnion. In November 2007, we received a response letter from the FDA requesting additional analyses and data regarding our marketing application for Synvisc-One in the U.S.United States. We plan to respond to the FDA in the first half of 2007,2008 and we expect to launch this productregulatory action on our application in the European Union by the end of 2007 and in the United States in the firstsecond half of 2008.
Sepra Products. The Sepra family of products is aimed primarily at preventing adhesions (internal scar tissue) following various surgical procedures in areas of the body such as the abdomen and pelvis. These products are produced from biomaterials derived from hyaluronan. We market the Sepra products primarily through a direct sales force in the U.S.,United States, France and Australia, and primarily through distribution arrangements in Japan and the rest of the world. Our Sepramesh IP hernia mesh product is marketed by Davol, Inc., a subsidiary of C.R. Bard, Inc., under a license agreement.
Seprafilm, the first marketed product and largest by sales volume of the Sepra family, is the only FDA-approved product clinically proven to reduce the incidence, extent and severity of postsurgical adhesions in both the abdomen and pelvis. There are approximately 2 million applicable abdominal and pelvic procedures performed annually in the U.S.,United States, including 1.1 million Caesarean sections, a largely untapped market. During 2005, we launched Sepramesh IP, a second generation product for hernia repair to replace Sepramesh, which has been on the market since 2000.
Genetics
We develop and provide high quality, sophisticated and complex reproductive testing services primarily in the U.S.United States and Japan. In the U.S.,United States, we also offer diagnostic services for reproductive markets (primarily
pre-natal, post-natal and infertility areas) and for the oncology andmarket. We also offer genetic counseling services focused on pre-natal and post-natal care,in the reproductive and fertility medicine.area. We offer several types of testing—the most significant are cytogenetic testing, molecular genetic (DNA) testing, immunohistochemistry testing, flow cytometry testing and biochemical testing. These services are promoted through a direct sales force in the U.S.,United States, with testing performed in our nineeight major clinical laboratories located throughout the U.S.United States. We service the Japanese market through a direct sales force and distributors, with testing primarily performed in U.S. laboratories.
Oncology
Campath (alemtuzumab). Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). In September 2007, the FDA approved a supplemental biologics license application (sBLA) for Campath and approved expanded labeling for Campath to include first-line treatment of B-CLL. We estimate that there are over 13,000 patients in the United States now eligible to receive the product. In December 2007, we also received European approval of an expanded indication. Campath is marketed by Bayer HealthCare Pharmaceuticals Inc. (Bayer) in the United States as Campath and outside the United States as MabCampath. The product is sold commercially in over 60 countries.
Alemtuzumab for Multiple Sclerosis. Together with Bayer, we have begun enrolling patients in two phase 3 trials to measure alemtuzumab's comparative effect on disability accumulation and relapse rate versus Rebif across a two year period. One study includes previously untreated patients and one includes patients whose disease remains active following treatment with an approved therapy.
Clolar (clofarabine). Clolar is indicated in the United States for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) after at least two prior regimens. An estimated 300 children experience a second relapse and require therapy every year in the United States. We market clofarabine under the brand name Clolar in North America. In October 2007, with our acquisition of Bioenvision, we acquired worldwide rights to clofarabine. Clofarabine has approval in 27 European countries for the treatment of pediatric ALL patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response. We market clofarabine primarily through a direct sales force focused on hematologists and oncologists in the hospital setting, except in Australia and New Zealand where the product is marketed by a distributor.
We are developing the intravenous formulation of Clolar for significantly larger indications, including first-line and relapsed or refractory acute myeloid leukemia (AML) in adults. We are also developing an oral formulation of Clolar and have initiated clinical laboratorytrials for the treatment of myelodysplastic syndrome (MDS). Clolar has been granted orphan drug status for ALL and AML in Santa Fe, New Mexico.both the United States and European Union.
We are engaged in segments of the human healthcare products and services industry that are extremely competitive. Our competitors in the U.S.United States and elsewhere include major pharmaceutical, biotechnology, diagnostic testing and medical device companies. Some of these competitors may have more extensive research and development, regulatory, manufacturing, production, and sales and marketing capabilities. Some competitors may have greater financial resources. These companies may succeed in developing products and services that are more effective than any that we have or may develop and may also prove to be more successful than we are in manufacturing, marketing and selling products and services. In addition, technological advances or different approaches developed by one or more of our competitors may render our products and services obsolete, less effective or uneconomical. Each of our products and services faces different competitive challenges, and we describe many of them below.
Renal
Renagel. Renagel/Renvela. Renagel is aand Renvela are phosphate binderbinders for the treatment of hyperphosphatemia andhyperphosphatemia. Renagel is the most prescribed phosphate binder in the U.S.United States. Phosphate binders such as Renagel, are currently the only available treatment for hyperphosphatemia, or elevated serum phosphorus levels in CKD patients on dialysis. There are several phosphate bindersbinder options available, including PhosLo®PhosLo®, a prescription calcium
acetate preparation sold by Fresenius Medical Care, and Fosrenol® (lanthanum carbonate)Fosrenol®, a prescription lanthanum carbonate sold by Shire. Other products used as phosphate binders include over-the-counter calcium-based antacids such as TUMS®TUMS® and metal-based options such as aluminum and magnesium. The doses necessary for calcium products to achieve adequate reductions in phosphate absorption can lead to harmful side effects such as hypercalcemia. Evidence suggests that increasing doses of calcium-based binders may lead to cardiac calcification. Aluminum hydroxide, a metal-based treatment option, is more effective at lowering phosphorus, but it is infrequently used because aluminum absorbed from the intestinal tract accumulates in the tissues of patients with chronic kidney failure, causing aluminum-related osteomalacia, anemia and dementia. Another metal-based option, Shire’sShire's Fosrenol, marketed in the U.S. and some European countries, is an effective phosphate binder but with limited long-term safety data. Several animal studies suggest lanthanum absorption may lead to harmful toxicities.
Hectorol. Dialysis providers typically select which therapy a CKD patient receives to treat secondary hyperparathyroidism based on safety, efficacy and cost. Abbott Laboratories, Inc., or Abbott, markets intravenous calcitriol (brand name Calcijex®Calcijex®) and intravenous paricalcitol (brand name Zemplar®Zemplar®) for end-stage renal disease patients. Current intravenous versions of these drugs are approved to manage secondary hyperparathyroidism in end-stage renal disease patients in the U.S.United States, Europe, and in European countries.major Latin American markets. A number of companies have launched or are planning to launch generic intravenous calcitriol in the U.S.United States. In 2005, Abbott received approval to market oral paricalcitol (Zemplar) in the U.S.United States for patients with stages 3 and 4 CKD. Since 2004, Amgen, Inc. has been marketing in the U.S.United States an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in patients with CKD on dialysis. The majority of patients studied on this calcimimetic agent were also taking vitaminVitamin D hormone to treat secondary hyperparathyroidism. Roche Pharmaceuticals, a division of F. Hoffman-LaRoche Ltd. (Roche), markets oral calcitriol (brand name Rocaltrol®Rocaltrol®) and Teva Pharmaceuticals Industries Ltd., or Teva, markets generic oral calcitriol in the U.S.United States to manage secondary hyperparathyroidism in CKD patients. These two products are approved in the U.S.United States for the treatment of elevated parathyroid hormone in both end-stage renal disease and pre-dialysis CKD.
Therapeutics
Cerezyme. Zavesca® Zavesca® is currently the only other marketed product aimed at treating Gaucher disease, however, we are aware of other on-going development efforts directed towards the treatment of the disease. Zavesca is a small molecule oral therapy developed by CellTech Group plc, which was acquired by UCB S.A. in 2004, and marketed by Teva in Israel and Actelion Ltd. in the U.S.United States and the European Union. Zavesca has been approved for use in patients with mild to moderate Type 1 Gaucher disease for whom enzyme replacement therapy is unsuitable. To date, virtually all Gaucher disease patients who have received enzyme therapy have experienced strong clinical benefits with few side effects, so we do not expect the competition from Zavesca to have a significant impact on our sales of Cerezyme. We are aware of other on-going development efforts directed towards the treatment of the disease. Shire has conductedPharmaceuticals Group plc is conducting a phase 1/23 clinical trial for its gene-activated human glucocerebrosidase (GA-GCB) product. Shire reported top-line data from this study and announced the initiation of a phase 3 study in the first quarter of 2007. In addition, Protalix Biotherapeutics Ltd. reported thathas initiated a phase 13 trial with their plant-derived human glucocerebrosidase (prGCB) therapy (expressed and purified in a bioreactor system from transformed carrot cells) indicated its short term safety in healthy normal volunteers. A phase 3 trial is expected to begin in 2007.. Lastly, Amicus Therapeutics, Inc. also has announced plans to begin ais conducting two phase 1 trial2 trials using Plicera, an experimental oral pharmacological chaperone (AT-2101) infor the first halftreatment of 2007.Gaucher disease. Other competitors could develop competitive products based on protein replacement therapy, small molecule or gene therapy approaches. Orphan drug status for Cerezyme, which provided us with exclusive marketing rights for Cerezyme in the U.S. for seven years, expired in 2001. However, we continue to have patents protecting our method of manufacturing Cerezyme until 2010 and the composition of Cerezyme as made by that process until 2013.
Fabrazyme. Fabrazyme has marketing exclusivity in the U.S.United States until 2010 due to its orphan drug status. Replagal®Replagal®, Shire’sShire's enzyme replacement therapy for Fabry disease, competes with Fabrazyme in the European Union, Australia, Canada, Japan, Iceland, Israel, New Zealand, Norway, Romania, Switzerland, Brazil and Taiwan. Transkaryotic Therapies, Inc., prior to its acquisition by Shire, publicly announced that it had abandoned its efforts to obtain marketing approval in the U.S. In addition, Amicus Therapeutics is conducting two phase 2 studies of aAmigal, its experimental small molecule pharmacological chaperone treatment for Fabry disease, one in males and another in females.disease.
Thyrogen. Thyrogen has no competitive product in the market. The medical alternative to Thyrogen is to withdraw the patient from thyroid hormone replacement therapy, which makes the patient hypothyroid and may cause many of the co-morbidities associated with hypothyroidism.
Myozyme. Myozyme has marketing exclusivity in the U.S.United States until 2013 and in the European Union until 2016 due to its orphan drug status. Amicus Therapeutics is conducting ahas completed two phase 1 study ofclinical studies for a small molecule treatment for Pompe disease.disease and has announced their plans to initiate a phase 2 clinical trial in early 2008.
Aldurazyme. Aldurazyme has marketing exclusivity in the U.S.United States until 2010 and in the European Union until 2013 due to its orphan drug status.
Transplant
Thymoglobulin and Lymphoglobuline. Thymoglobulin.Several companies market products used for the prevention and treatment of acute rejection in renal transplant. These products include Novartis AG’s Simulect®AG's Simulect®, Pfizer Inc.’s ATGAM®'s ATGAM®, Ortho Biotech’sBiotech's Orthoclone OKT®OKT®3, Fresenius Biotech GmbH’sGmbH's ATG-Fresenius S®S® and the Roche Group’s Zenapax®Group's Zenapax®. Competition in the acute transplant graft rejection market is largely driven by product efficacy due to the potential for decreased long term survival of transplanted organs as the result of an acute organ rejection episode.
Biosurgery
Synvisc.Current competition for Synvisc and Synvisc-One includes Supartz®Supartz®, a product manufactured by Seikagaku Kogyo that is sold in the U.S.United States by Smith & Nephew Orthopaedics and in Japan by Kaken Pharmaceutical Co. under the name Artz®Artz®; Hyalgan®Hyalgan®, produced by Fidia S.p.A. and marketed in the U.S.United States by Sanofi-Aventis; Orthovisc®Orthovisc®, produced by Anika
Therapeutics, Inc., marketed in the U.S. by Johnson & Johnson and marketed outside the U.S.United States through distributors; Euflexxa™, a product manufactured and sold by Ferring Pharmaceuticals in the U.S.United States and Europe; and Durolane®Durolane®, manufactured by Q-Med AB and marketed outside the U.S.United States by Smith & Nephew Orthopedics. Durolane and Euflexxa, the most recently approved products in Europe and the U.S.,United States, respectively, are produced by bacterial fermentation, as opposed to Synvisc, which is avian-sourced. In addition, the treatment protocol for Durolane is a single-injection, as comparedsingle-injection. We have received approval to Synvisc’s current three injection regimen (although it offers a shorter duration of pain relief).market Synvisc-One in the European Union and are pursuing its approval in the United States. Production via bacterial fermentation and treatment with a reduced number of injections may represent a competitive advantagesadvantage for these products. We are aware of various viscosupplementation products on the market or in development, but are unaware of any products that have physical properties of viscosity, elasticity or molecular weight comparable to those of Synvisc. We are also unaware of any products that achieve our duration of efficacy with only three injections.
Sepra Products.The Sepra products face competition from other adhesion prevention technologies. Another competitive factor affecting the adoption of Sepra products is the extent to which surgeons continue to treat patient conditions using procedures for which the Sepra products are indicated. For example, Seprafilm adhesion barrier is not indicated for use in laparoscopic procedures, so adoption by surgeons of new laparoscopic procedures could have the effect of limiting Seprafilm adhesion barrier adoption.
13
Seprafilm does not have significant on label direct competition in the area of abdominal surgery in the U.S.,United States, but does compete with other products in other indications. Innovata plc has received FDA approval of Adept®,Baxter Healthcare currently markets Adept® Adhesion Reduction Solution, which is a liquid solution for adhesion reduction,approved in the U.S.United States for gynecologic laparoscopic adhesiolysis indications and has begun marketing the product through a global distribution agreement with Baxter.adhesiolysis. The labeled indications for Seprafilm and Adept are mutually exclusive, though off-label use of each may result in limited competition. Gynecare Worldwide, a division of Ethicon, Inc., a Johnson & Johnson company, markets Interceed®Interceed®, a sheet adhesion barrier similar in intended use to Seprafilm, but is indicated only for selected open gynecological indications.procedures. In Japan, Seprafilm competes only with Interceed. Outside the U.S.United States and Japan, Seprafilm competes with several adhesion prevention products. Innovata’sBaxter Healthcare's Adept solution is approved in the European Union for abdominal and gynecological surgeries. FzioMed, Inc. has received CE Mark approval in the European Union for Oxiplex®Oxiplex®/AP Gel, an adhesion barrier for abdominal/pelvic surgery, and is conducting a pivotal clinical trial in the U.S. Fziomed has announced a global distribution agreement with Ethicon for distribution of Oxiplex/AP Gel. Confluent Surgical, Inc.’sCovidieu's Spraygel™, an adhesion barrier used in abdominopelvic procedures, is approved for sale in Europe. MAST Biosurgery AG’sAG's bioresorbable film product, SurgiWrap™, is also CE marked with an indication for abdominal and pelvic adhesion prevention, but holds an FDA clearance as a surgical mesh in the U.S. Life Medical Sciences, Inc. is developing several adhesion prevention products, including REPEL™ for gynecologic surgery and REPEL-CV™ for cardiovascular surgery.to reduce adhesions following pediatric cardiac procedures. In addition, FzioMed’s Oxiplex®FzioMed's Oxiplex®/SP Gel, an adhesion barrier for spine surgery, is approved for sale in the European Union and in other countries outside the U.S.United States.
Genetics
The U.S. market for genetic and complex testing is highly competitive and is divided among many laboratories, the largest of which are Quest Diagnostics and Laboratory Corporation of America Holdings (LabCorp). In addition, many hospitals provide some or all of these services through their in-house laboratories. Competitive factors in the genetic and complex testing and diagnostic services business generally include reputation of the laboratory, range of services offered, pricing, managed care contracts, convenience of sample collection and pick-up, quality of analysis and reporting, timeliness of delivery of completed reports and levels of automation and information technology solutions.
Oncology
Campath. Campath has become a well-established therapy for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) patients since its initial FDA approval in May 2001 as the only monoclonal antibody therapy indicated for the treatment of CLL. Other therapies administered to patients with relapsed or refractory CLL include combination chemotherapy regimens and rituxamab, which is marketed by Biogen Idec, Inc. and Genentech, Inc. in the United States and Roche outside of the United States as Rituxan and MabThera, respectively. The use of Campath as an initial therapy for CLL has increased following the FDA approval expanding Campath's indication to include all lines of CLL therapy. Other therapies under clinical study for the treatment of CLL include bendamustine, oblimersen, ofatumumab, lumiliximab and lenalidomide.
Clolar. Since FDA approval in December 2004, Clolar has penetrated significantly into its labeled indication for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory ALL after at least two prior regimens. Other therapies available for patients in second relapse include cytarabine and mitoxantrone. These agents are available as generics with no significant commercial promotion. Arranon (nelarabine), marketed by GlaxoSmithKline, is indicated for the treatment of patients with T-cell ALL whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. T-cell ALL is estimated to represent less than 20% of pediatric ALL patients. There are a limited number of anti-cancer agents in clinical trials for the treatment of relapsed pediatric ALL patients, including epratuzamab, which is being developed by Immunomedics, Inc.
Patents, License Agreements and Trademarks
In general, we pursue a policy of obtaining patent protection both in the U.S.United States and in selected countries outside the U.S.United States for subject matter we consider patentable and important to our business. Patents owned by us that we consider material include the following:
Renal
Renagel is protected by U.S. Patent Nos. 5,667,775 which expires on September 16, 2014; 5,496,545, 6,509,013 and 7,014,846 which expire on August 11, 2013; 6,733,780, which expires on October 18, 2020; and corresponding international counterparts. Renvela is protected by U.S. Patent Nos. 5,667,775 which expires on September 16, 2014; 5,496,545, 6,509,013 and 7,014,846 which expire on August 11, 2013; 6,858,203 which expires on September 20, 2013 and corresponding international counterparts. Hectorol is protected by U.S. Patent Nos. 6,903,083 which expires on July 18, 2021; 5,602,116 which expires on February 11, 2014; 5,707,980 which expires on August 17, 2010;and 5,869,473 which expiresexpire on August 2, 2008; 5,869,472 which expires on July 18, 2014,February 9, 2016, and corresponding international counterparts.
Therapeutics
Cerezyme is protected by U.S. Patent Nos. 5,236,838 which expires on August 17, 2010; 5,549,892 which expires on August 27, 2013; 6,451,600 which expires on September 17, 2019; and corresponding international counterparts. Myozyme is protected by U.S. Patent No. 6,118,045 which expires on July 31, 2016; and corresponding international counterparts. Thyrogen is protected by U.S. Patent Nos. 5,240,832 and 5,674,711 which expire on August 31, 2010; 5,602,006 which expires on February 11, 2014; 5,658,760, which expires on August 19, 2014; and corresponding international counterparts.
Biosurgery
Synvisc is protected by U.S. Patent Nos. 5,143,724 which expires on August 8, 2011; 5,399,351 which expires on March 21, 2012; and corresponding international counterparts. Seprafilm is protected
by U.S. Patent Nos. 5,017,229 which expires on May 21, 2008; 5,527,893 which expires on June 18, 2013; 6,235,726 which expires September 18, 2007; and corresponding international counterparts.
Genetics
Genetic testing services, e.g. for Cystic Fibrosis, are protected by U.S. Patent Nos. 5,585,3305,589,330, 5,834,181 and 5,834,1815,849,483 which expire on July 28, 2014; 5,849,483 which expires December 15, 2015; 5,882,856 which expires March 16, 2016;and 6,207,372 which expires June 6,expire on March 16, 2016; and corresponding international counterparts.
In addition, a portion of our proprietary position is based upon patents that we have licensed from others either through collaboration or traditional license agreements, including patents relating to:
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- Fabrazyme;
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- Thyrogen;
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- Aldurazyme;
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- Myozyme;
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- Campath;
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- Clolar; and
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- genetic testing.
These collaboration and license agreements generally require us to share profits with our collaborative partners or pay royalties to our licensors upon commercialization of products covered by the licensed technology.
Generally, patents issued in the U.S.United States are effective for:
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- the longer of 17 years from the date of issue or 20 years from the earliest effective filing date of the corresponding patent application if filed prior to June 8, 1995; and
· - •
- 20 years from the earliest filing date for patent applications filed on or after June 8, 1995.
In some cases, the patent term can be extended to recapture a portion of the term lost during FDA regulatory review. The duration of foreign patents varies in accordance with local law.
We also rely on trade secrets, proprietary know-how and continuing technological innovation to develop and maintain a competitive position in our product areas. We require our employees, consultants and corporate partners who have access to our proprietary information to sign confidentiality agreements.
Our patent position and proprietary technology are subject to certain risks and uncertainties. We have included information about these risks and uncertainties in Item 1A., “Risk"Risk Factors,”" of this report. We encourage you to read that discussion, which we are incorporating into this section by reference.
Our products and services are sold around the world under brand-name trademarks and service-marks. Trademark protection continues in some countries as long as the mark is used; in other countries, as long as it’sit's registered. Registrations generally are for fixed, but renewable, terms. We consider our registered trademarks Genzyme®Genzyme®, Cerezyme®Cerezyme®, Ceredase®Ceredase®, Fabrazyme®Fabrazyme®, Thyrogen®Thyrogen®, Myozyme®Myozyme®, Renagel®Renagel®, Campath®Renvela®, MabCampath®Hectorol®, Clolar®Thymoglobulin®, Synvisc®Campath®, Carticel®MabCampath®, MACI®Clolar®, GlucaMesh®Evoltra®, GlucaTex®Synvisc®, Seprafilm®Carticel®, Sepragel®MACI®, Seprapack®GlucaMesh®, Sepramesh®GlucaTex®, Hylaform®Sepra®, Hylashield®Seprafilm®, Hylasome®Sepragel®, Captique®Seprapack®, Epicel®Sepramesh®, OSOM®Sepraspray®, N-geneous®Hylaform®, GlyPro®Hylashield®, InSight®Lipobridge® Captique®, AFP3®Epicel®, AFP4®OSOM®, N-geneous®, Direct LDL®, GlyPro®, InSight®, AFP3®, and Hectorol®AFP4®, together with our trademarks, VERIGEN™, Thymoglobulin™, Lymphoglobuline™, Mozobil™, Cholestagel™, Renvela™,
CF87™, Sepra™, Hylashield Nite™, SAGE™, LongSAGE™
and SPHERE™, and BioMarin/Genzyme LLC’sLLC's registered trademark, Aldurazyme®Aldurazyme®, in the aggregate, to be of material importance to our business.
Regulation by governmental authorities in the U.S.United States and other countries is a significant factor in the development, manufacture, commercialization, pricing and reimbursement of our products and services.
FDA Regulation
Most of our products and services require approval from the FDA and corresponding agencies in other countries before they can be marketed. In the U.S.,United States, we market products that the FDA classifies as either “drugs,” “biologics”"drugs," "biologics" or “devices.”"devices." The activities required before drugs or biologics may be marketed in the U.S.United States include:
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·preclinical laboratory tests,in vitro andin vivo preclinical studies and formulation and stability studies;·- •
- the submission to the FDA of an application for human clinical testing, which is known as an Investigational New Drug (IND) application;
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- adequate and well controlled human clinical trials to demonstrate the safety and effectiveness of the drug or biologic;
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- the submission of
an NDAa New Drug Application (NDA) for a drug or a Biologics License Application (BLA) for a biologic; and· - •
- the approval by the FDA of the NDA or BLA.
As part of product approval, the manufacturer of the product must undergo a pre-approval Good Manufacturing Practices inspection (for a drug or biologic) from the FDA. Since any approval granted by the FDA is both site and process specific, any material change by a company in the manufacturing process, equipment or location may necessitate additional FDA review and approval.
In addition, the FDA may grant accelerated approval for drugs and biologics on the basis of a surrogate endpoint reasonably likely to predict clinical benefit. In such cases, we are required to conduct post-approval clinical studies to confirm the clinical benefit of the surrogate endpoint that was the basis of the accelerated approval. These clinical studies require the collection of additional data before full approval will be given and can often be long-term commitments. Although the FDA has not historically invoked its authority to withdraw an accelerated approval, it may do so. We currently have a number of products approved under the accelerated approval mechanism.
Products that are classified as devices also require some form of FDA approval prior to marketing. Devices are classified as Class I, II or III, depending upon the information available to assure their safety and effectiveness. In general, Class I and Class II devices are devices whose safety and effectiveness can reasonably be assured through general or specific controls, respectively. Class III devices are life sustaining, life supporting, are of substantial importance in preventing impairment to health or pose an unreasonable risk of adverse effect. They are implantable devices or new devices which have been found not to be substantially equivalent to legally marketed devices. The steps required for approval of a Class III device include:
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·preclinical laboratory tests andin vitro andin vivo preclinical studies;·- •
- the submission to the FDA and approval of an Investigational Device Exemption (IDE) application to allow initiation of clinical testing;
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- human clinical studies to prove safety and effectiveness of the device;
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- the submission of a Pre-Marketing Approval application (PMA); and
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- the approval by the FDA of the PMA.
Typically, clinical testing of devices involves initial testing to evaluate safety and feasibility and expanded trials to collect sufficient data to prove safety and effectiveness. In addition, the procedures and the facilities used to manufacture the device are subject to review and approval by the FDA.
A device (other than a Class III device) that is proven to be substantially equivalent to a device marketed prior to May 28, 1976, when government regulations for devices were first introduced, can be marketed after clearance of a 510(k) application rather than the filing of an IDE application and a PMA. The 510(k) application must contain a description of the device, its methods of manufacture and quality control procedures and the results of testing to demonstrate that the device is substantially equivalent to the device already marketed.
The time and expense required to perform the clinical testing necessary to obtain FDA approval for regulated products can frequently exceed the time and expense of the research and development initially required to create the product. Even after initial FDA approval has been obtained, we could very likely be required to conduct further studies to provide additional data on safety or efficacy or, should we desire, to gain approval for the use of a product as a treatment for additional clinical indications. In addition, use of these products during testing and after marketing approval has been obtained could reveal side effects which, if serious, could limit uses, require a Risk Evaluation & Mitigation Strategy or in the most serious cases, result in a market withdrawal of the product or expose us to product liability claims. We are also subject to monetary penalties if we do not meet the timelines agreed to with the FDA for these post-approval requirements.
Regulation Outside of the U.S.United States
For marketing outside the U.S.,United States, we are subject to foreign regulatory requirements governing human clinical testing and marketing approval for our products. These requirements vary by jurisdiction, differ from those in the U.S.United States and may require us to perform additional pre-clinical or clinical testing regardless of whether FDA approval has been obtained. The amount of time required to obtain necessary approvals may be longer or shorter than that required for FDA approval. In many countries outside of the U.S.,United States, coverage, pricing and reimbursement approvals are also required.
Our initial focus for obtaining marketing approval outside the U.S.United States is typically the European Union. European Union regulations and directives generally classify health care products either as medicinal products, medical devices orin vitro diagnostics. For medicinal products, marketing approval may be sought using either the centralized procedure of the EMEA or the decentralized, mutual recognition process. The centralized procedure, which is mandatory for biotechnology derived products, results in a recommendation in all member states, while the European Union mutual recognition process involves country-by-country approval.
European Union regulations for products classified as medical devices have been implemented. Devices, such as our Sepra products, must receive marketmarketing approval through a centralized procedure in which the device receives a CE Mark allowing distribution to all member states of the European Union. The CE Mark certification requires us to receive International Standards Organization certification for each facility involved in the manufacture or distribution of the device. This certification comes only after the development of an all inclusive quality system, which is reviewed for compliance to International Quality Standards by a licensed “Notified Body”"Notified Body" working within the European Union. After certification is received, a product dossier is reviewed that attests to the product’sproduct's compliance with European Union directive 93/42 EEC for medical devices. Only after this point is a CE Mark granted.
Other Government Regulation
Good Manufacturing Practices.All facilities and manufacturing techniques used for the manufacture of Genzyme’sGenzyme's products must comply with applicable FDA regulations governing the production of pharmaceutical products known as “Good"Good Manufacturing Practices.”"
Orphan Drug Act.The Orphan Drug Act provides incentives to manufacturers to develop and market drugs for rare diseases and conditions affecting fewer than 200,000 persons in the U.S.United States at the time of application for orphan drug designation. The first developer to receive FDA marketing approval for an orphan drug is entitled to a seven year exclusive marketing period in the U.S.United States for that product. However, a drug that the FDA considers to be clinically superior to, or different from, another approved orphan drug, even though for the same indication, may also obtain approval in the U.S.United States during the seven year exclusive marketing period. We believe that the commercial success of our orphan drug products depends more significantly on the associated safety and efficacy profile and on the price relative to competitive or alternative treatments and other marketing characteristics of each product than on the exclusivity afforded by the Orphan Drug Act. Additionally, these products may be protected by patents and other means.
Legislation similar to the Orphan Drug Act has been enacted in other countries outside of the U.S.,United States, including the European Union. The orphan legislation in the European Union is available for therapies addressing conditions that affect five or fewer out of 10,000 persons. The market exclusivity period is for ten years, although that period can be reduced to six years if, at the end of the fifth year, available evidence establishes that the product is sufficiently profitable not to justify maintenance of market exclusivity.
Regulation of Diagnostic Testing Services.The Clinical Laboratories Improvement Act of 1967, as amended in 1988 (CLIA) provides for the regulation of clinical laboratories by the U.S. Department of Health and Human Services (HHS). All of our clinical laboratories are licensed by CLIA, approved licensed by the College of American Pathologists and certifiedlicensed by the appropriate state agencies. CLIA regulates virtually all clinical laboratories by requiring they be certified bylicensed with the federal governmentCenters for Medicare and Medicaid Services (CMS) and comply with various operational, personnel and quality requirements intended to ensure that their clinical laboratory testing services are accurate, reliable and timely. CLIA does not preempt state laws that are more stringent than federal law. For example, state laws may require additional personnel qualifications, quality control, validation, record maintenance and/or proficiency testing.
In the past, the The FDA has claimed regulatory authority over laboratory-developed tests, but has exercised enforcement discretion in not regulating most laboratory-developed tests performed by high complexity CLIA-certified laboratories.discretion. In December 2000, the HHS’s Secretary’sHHS's Secretary's Advisory Committee on Genetic Testing recommendedidentified gaps in the current oversight systems that the FDA be the lead federal agency to regulateplay a role in genetic testing. In late 2002, a new HHS Secretary’sSecretary's Advisory Committee on Genetics, Health and Society was appointed to replace the prior Advisory Committee, but it has not yet made any final recommendations.Committee(SACGHS). In November 2007, SACGHS issued a draft report for public comment "U.S. System of Oversight of Genetic Testing: A Response to the meantime,Charge of the Secretary of HHS".
In September 2007, the FDA is considering revising its regulations on analyte specific reagents, which are usedissued a final guidance regarding the manufacturing of Analyte Specific Reagents (ASR) for use in laboratory-developed tests, including laboratory-developed genetic testing, and establishing new regulatory guidelines for certain laboratory-developedlaboratory developed tests. The latter potentially could bring under the scopeguidance clearly defined requirements for quality systems, labeling, registering and marketing of FDA regulation some tests that currently can be used without FDA approval.ASRs. Increased FDA regulationenforcement regarding the manufacturing and sale of ASR reagents and increased enforcement regarding the sale of Research Use Only (RUO) and Investigational Use Only (IUO) reagents used in laboratory-developed testingand instruments for clinical diagnostic purposes could potentially lead to significant increased costs for manufacturing, and delays in introducingpossible supply interruptions as suppliers attempt to comply with these newly defined requirements. Collectively, these activities may impact the ability for a clinical laboratory to introduce new tests including genetic tests.or new technologies.
In addition, the Medicare and Medicaid programs provide a substantial portion of reimbursement for our diagnostic products. Whether these programs pay for any particular test, and the amounts that they pay, may be unilaterally changed at any time.
Regulation of Diagnostic Products.The FDA has regulatory responsibility over instruments, test kits, reagents and other devices used to perform diagnostic testing by clinical laboratories. Like other medical devices, in vitro diagnostic (IVD) products are divided into three classes according to the level of regulatory control needed to assure safety and effectiveness. Genzyme’sGenzyme's current IVD products are either Class I or Class II, and are either exempt from pre-market notification or require a 510(k) submission.
Regulation of Gene Therapy Products.In addition to FDA requirements, the National Institutes of Health have established guidelines providing that transfers of recombinant DNA into human subjects at NIH laboratories or with NIH funds must be approved by the NIH Director. The NIH has established the Recombinant DNA Advisory Committee to review gene therapy protocols. We expect that many of our gene therapy protocols will be subject to review by the Recombinant DNA Advisory Committee. In the United Kingdom, our gene therapy protocols will be subject to review by the Gene Therapy Advisory Committee and in Germany, these protocols will be subject to review by the Commission for Somatic Cell Therapy. Greater government regulation of gene therapy products may lead to regulatory delays, increased development costs, and negative public perception of the gene therapy products we are developing.
Clinical Trial Registries and Results Databases. Consistent with its long-standing commitment to transparency of relevant information about its products, Genzyme has exceeded previous legal requirements to register clinical trials. Since 2005, the company has posted information about ongoing and completed clinical trials on its own Web site and other widely accessible sites, including the NIH-sponsored http://www.clinicaltrials.gov.
In 2007, changes in both federal and state laws expanded the scope of trials requiring registration, increased the amount of information required to be included with the registration, and established new requirements for disclosing the results of completed trials. Although Genzyme has voluntarily provided a substantial portion of the newly required information, the recently enacted legislation (Food and Drug Administration Amendment Act of 2007, or the FDAAA of 2007) has triggered a revision of internal procedures to ensure compliance.
Specifically, the federal legislation requires disclosure of ongoing applicable clinical trials (including, for the first time, specified device trials as well as drug trials) in http://www.clinicaltrials.gov within 21 days of first patient enrolled and of all pediatric post market device surveillance studies. In addition, beginning September 2008, the existing clinical trials registry will be expanded to include a clinical trials results database. Full expansion is to be completed by September 2010. Results of completed applicable clinical trials must be disclosed in the results database within 1 year of trial completion, unless an extension is granted for pending regulatory action. The company will reassess its policies to ensure that all applicable trials are registered and results disclosed. Failure to meet the requirements can result in penalties including civil monetary penalties.
Pediatric Regulation. The FDAAA of 2007 reauthorized the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). BPCA continues to offer manufacturers a 6-month market exclusivity incentive to conduct pediatric clinical studies at the request of the FDA. PREA requires manufacturers to file pediatric assessments, which may include actual pediatric data, a deferral of the pediatric obligation, or a waiver of the pediatric requirement, at the time of filing for all new drug and biologic submissions, as well as for certain supplemental applications. Pursuant to PREA, the FDA has the authority to require sponsors to conduct pediatric research as a contingency of the approval of an application or supplement or as a post-approval commitment. Under both BPCA and
PREA, the FDA has the authority to mandate a pediatric label change subsequent to the filing of pediatric clinical data as well as publicly disseminate FDA reviews of pediatric clinical study data. The FDA's increased oversight and authority regarding pediatric studies and subsequent labeling changes may result in regulatory delays and additional development costs for Genzyme.
Other Laws and Regulations.Our operations are or may be subject to various federal, state and local laws, regulations and recommendations relating to the marketing of products and relationships with treating physicians, data protection, safe working conditions, laboratory and manufacturing practices, the export of products to certain countries, and the purchase, storage, movement, use and disposal of hazardous or potentially hazardous substances used in connection with our research work and manufacturing operations, including radioactive compounds and infectious disease agents. Although we believe that our safety procedures comply with the standards prescribed by federal, state and local regulations, the risk of contamination, injury or other accidental harm cannot be eliminated completely. In the event of an accident, we could be held liable for any damages that result and any liabilities could exceed our resources.
Sales Marketing and Product PricingMarketing
We are subject to various federal and state laws pertaining to health care “fraud"fraud and abuse,”" including anti-kickback and false claims statutes. Anti-kickback laws make it illegal for a prescription drug manufacturer to solicit, offer, receive, or pay any remuneration in exchange for, or to induce, the referral of business, including the purchase or prescription of a particular drug. The federal government has published regulations that identify “safe harbors”"safe harbors" or exemptions for certain payment arrangements that do not violate the anti-kickback statutes. Genzyme seeks to comply with the safe harbors where possible. Due to the breadth of the statutory provisions, and the lack of guidance in the form of regulations or court decisions addressing some industry activities, it is possible that our practices might be challenged under anti-kickback or related laws. False claims laws prohibit anyone from knowingly and willingly presenting, or causing to be presented for payment to third-party payors, including Medicare and Medicaid, claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed, or claims for medically unnecessary items or services. Promotion of drugs for uses outside their labeled indications, so called “off-label”"off-label" promotion, recently has led to several financially significant settlement agreements under the False Claims Act.
Our activities relating to the sale and marketing of, and price reporting for, our products are subject to scrutiny under these fraud and abuse laws. Violations of these laws may result in criminal and/or civil sanctions, including fines and civil monetary penalties, as well as possible exclusion from federal health care programs, including Medicare and Medicaid. Federal and state authorities are paying increased attention to the pharmaceutical and biotechnology industries in enforcement of these laws, and we have been named in several legal proceedings alleging violations.
Legislation and regulations have been enacted by, or are pending in, various states to regulate sales and marketing practices of pharmaceutical, biotechnology and medical device manufacturers. These initiatives generally involve limitations or prohibitions on, and reporting to state agencies of, financial interactions between manufacturers and health care practitioners. Similar initiatives have recently been introduced in Congress. We have dedicated resources that monitor these developments and work to comply appropriately with them.
In addition, federal and state laws have been enacted that require public disclosure on an internet-accessible registry of information describing human clinical trials of drugs, devices and biologics and a summary of the results of those company-sponsored studies. We previously disclosed voluntarily information about our ongoing clinical studies and have committed resources to comply with new clinical trial registry requirements.
Laws and regulations have been promulgated at federal and state levels in the United States and in foreign countries intended to combat counterfeit drug products or, in some foreign jurisdictions, to facilitate foreign country-specific pharmaceutical reimbursement programs. We comply with those federal, state and foreign "pedigree" or similar laws or rules to the extent currently in effect. We have allocated resources to develop interoperable electronic systems to comply with forthcoming product serialization and track and trace requirements.
Product Pricing
We participate in the Medicaid rebate program. Participation in this program has included extending comparable discounts under the Public Health Service (PHS) pharmaceutical pricing program. Under the Medicaid rebate program, we pay a quarterly rebate for each unit of drug product that is reimbursed by Medicaid. The amount of the rebate for each product is set by law as a minimum 15.1% of the average manufacturer price (AMP) of that product, or if it is greater, the difference between AMP and the best price available from Genzyme to any customer. The rebate amount also includes an inflation adjustment if AMP increases greater than inflation. The PHS pricing program extends discounts comparableinflation adjustment can cause the rebate amount to be significantly higher than the Medicaidminimum 15.1% rebate to a variety of community health clinics and other entities that receive health services grants from the PHS, as
well as hospitals that serve a disproportionate share of poor Medicare and Medicaid beneficiaries.mentioned above, particularly following our periodic price increases. The rebate amount is recomputed each quarter based on our reports of our current AMP and best price for each of our products. In addition, we are required to report AMP on a monthly basis. Computations are based on complex rules issued by the Medicaid program informally in the past and formalized in 2007 by regulations that went into effect October 2007. We have policies and procedures in place that we update as Medicaid guidance changes and we have updated our policies and procedures to be consistent with the new regulations. We follow those policies and procedures when calculating our AMPs and BPs. The terms of our participation in the Medicaid program impose an obligation to correct the prices reported in previous months and quarters, if necessary. Any such corrections could result in an overage or underage in our rebate liability for past quarters, depending on the nature of the correction. In addition to retroactive rebates (and interest, if any), if we were found to have knowingly submitted false information to the government, in addition to other penalties available to the government, the statute provides for civil monetary penalties for each claim containing false information. In addition, the minimum discount of 15.1% could be increased by Congress in the future, thereby increasing our discounts to the Medicaid program and to other entities that receive discounts comparable to the Medicaid rebate.
Participation in the Medicaid rebate program has included extending comparable discounts under the Public Health Service (PHS) pharmaceutical pricing program. The PHS pricing program extends discounts to community health clinics and other entities that receive health services grants from the PHS, as well as hospitals that serve a disproportionate share of poor patients. Failure to extend mandated discounted pricing to eligible providers exposes us to retroactive pricing corrections and penalties.
Medicare Part B covers drugs that are administered by physicians, including our injected and infused drugs. Medicare reimburses physicians and others who purchase our Part B covered drugs an amount equal to the drug's average sales price plus 6% (ASP+6%). Medicare has issued regulations and other guidance on how manufacturers are to calculate ASP. We have policies and procedures in place that are consistent with the Medicare rules and we calculate ASPs every quarter in accordance with those policies and procedures. Medicare uses our calculated ASPs to set reimbursement. If we were to miscalculate ASP, then Medicare reimbursement also would be incorrect and we would be exposed to potential penalties such as those described in the Medicaid rebate program description above.
Part D of the MedicaidMedicare Prescription Drug, Improvement and Modernization Act of 2003, or Medicare Part D, also has made Medicareprovides coverage available for the first time forself-administered drugs such as pills, tablets and creams, that do not need to be injected or infused by a number of drugs,physician, including Renagel and oral Hectorol beginning in 2006.Hectorol. However, Medicare Part D is administered by private vendors under contract with the U.S. government. Each government and each
vendor establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the vendor may modify from time-to-time. Renagel and Hectorol currently are well-positioned on the majority of formularies of nation-wide prescription drug plans participating in the Medicare Part D program as well as many of the large regional plans. The U.S. Congress could also significantly change the Medicare Part D program in the future, including requiring the federal government to negotiate discounts for our drugs or matching mandatory discounts to those required in other federal programs.
Genzyme also is required to offer discounted pricing to federal agencies via the Federal Supply Schedule (FSS). FSS pricing is negotiated periodically with the Department of Veterans Affairs (VA). Although FSS pricing is negotiated, it is intended to not exceed the price that we charge our most-favored non-federal customer for the drug. The minimum discount is statutorily set at approximately 24%. However, an inflation penalty applies and can cause the discount to increase significantly, particularly following our periodic price increases. The VA has issued complex regulations and other guidance on how manufacturers are to calculate annual increases in the FSS prices. We have policies and procedures in place that are consistent with these complex VA rules and we calculate FSS prices every quarter in accordance with those policies and procedures. If we were to miscalculate FSS prices, then federal agencies would pay incorrect amounts for our drugs and we would be exposed to potential penalties, including ineligibility of our drugs for reimbursement by any federal agency, state Medicaid programs and the PHS, and possibly false claims liability.
In December 2007, Congress passed legislation extending FSS pricing to the TriCare retail program, which provides reimbursement for military personnel and their dependents when they purchase drugs from retail pharmacies instead of at military pharmacies. Previously, The Department of Defense was eligible for FSS pricing only on drugs dispensed by their military pharmacies and not on drugs dispensed by retail pharmacies.
Outside the United States our products are paid for by a variety of payers. In many countries governments are primarily responsible for reimbursing for our products. Governments often have significant discretion in determining whether a product will be reimbursed at all, and if it is, how much will be paid.
As of December 31, 2006,2007, we, together with all of our consolidated subsidiaries, had approximately 9,00010,000 employees worldwide.
Financial Information Regarding Segment Reporting
We have provided the information required by Item 101(b) of Regulation S-K in Note Q., “Segment"Segment Information,”" to our Consolidated Financial Statements in the 20062007 Genzyme Corporation Annual Report set forth in Exhibit 13 to this Annual Report on Form 10-K. We are incorporating that information into this section by reference.
Research and Development Costs
We have provided the information required by Item 101(c)(1)(xi) of Regulation S-K in Part II, Item 8, “Financial"Financial Statements and Supplementary Data,”" and specifically in the Genzyme Corporation and Subsidiaries Consolidated Statements of Operations and Comprehensive Income and in Note I., “Investments"Investments in Marketable Securities and Strategic Equity Investments”Investments" to our Consolidated Financial Statements in the 20062007 Genzyme Corporation Annual Report set forth in Exhibit 13 to this Annual Report on Form 10-K. We are incorporating that information into this section by reference.
Sales by Geographic Area, Significant Customers and Products
We have provided the information required by Items 101(c)(1)(i) and (vii) and 101(d) of Regulation S-K in the 20062007 Genzyme Corporation Annual Report under the heading “Management’s"Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries’Subsidiaries' Financial Condition and Results of Operations”Operations" and in Note Q., “Segment"Segment Information,”" to our Consolidated Financial Statements in the 2007 Genzyme Corporation Annual Report set forth in Exhibit 13 to this Annual Report on Form 10-K. We are incorporating that information into this section by reference.
20
We file electronically with the SEC our annual report on Form 10-K, our quarterly reports on Form 10-Q, and current reports on Form 8-K pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934. You may read or copy any materials we file with the SEC at the SEC’sSEC's Public Reference Room at 100 F Street, N.E., Washington, D.C. 20549. You may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. The SEC also maintains an Internet site that contains reports, proxy and information statements, and other information about issuers that file reports electronically with the SEC. The address of that site is http://www.sec.gov.
You may obtain a free copy of our annual report on Form 10-K, our quarterly reports on Form 10-Q and current reports on Form 8-K, and amendments to those reports, as soon as reasonably practicable after we file them with the SEC, on our website at http://www.genzyme.com or by contacting our Investor Relations department at 1-617-252-7570. The reference to our website is not intended to incorporate information on our website into this document by reference.
We incorporate our disclosure related to risk factors into this section by reference from the 20062007 Genzyme Corporation Annual Report under the heading “Management’s"Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries’Subsidiaries' Financial Condition and Results of Operations—Risk Factors,”" which is included in Exhibit 13 to this Annual Report on Form 10-K.
ITEM 1B. UNRESOLVED STAFF COMMENTS
None.
Our operations are conducted in manufacturing, warehousing, development/clinical plant, clinical laboratories, and research and office facilities that are located principally in: the U.S.;United States; the United Kingdom; the Republic of Ireland; The Netherlands; Belgium; France; Canada; Switzerland; Germany; and Australia.
We lease all of our facilities except for certain facilities in:
·
- •
- Geel, Belgium (land subject to 99 year leasehold);
· - •
- Haverhill and Maidstone, England;
· - •
- Allston (land subject to 65 year leasehold), Framingham and Waltham, Massachusetts; Ridgefield, New Jersey; and Santa Fe, New Mexico in the
U.S.;United States; and· - •
- Waterford, Ireland (land subject to 999 year leasehold).
Our principal manufacturing facilities are used for the large-scale production of therapeutic proteins and enzymes, including Cerezyme, Fabrazyme, Myozyme and Thyrogen; renal products,
including Renagel;Renagel and Renvela; and immunosuppressive agents, including Thymoglobulin, and Lymphoglobuline, biomaterials, including Synvisc and the Sepra family of anti-adhesion products, bulk hyaluronic acid, cellhuman-cell processing services, including Carticel, MACI, and Epicel and genetic testing services. The facilities also are used for the receipt of contract manufactured products and materials for Hectorol, Renagel, Campath, Clolar, Cholestagel and Clolar.Mozobil. We are also producing late-stage clinical materials, using gene therapy, at our gene therapy operations facility in San Diego, California. We believe that we have, or are in the process of developing or acquiring, adequate manufacturing capacity to support our requirements for the next several years.
Our administrative activities are concentrated at facilities we have leased in Cambridge and Framingham, Massachusetts and San Antonio, Texas in the U.S.;United States; Naarden, The Netherlands;Netherlands, Tokyo, Japan and Tokyo, Japan.Rio de Janeiro, Brazil. Our sales and marketing activities are principally located in Cambridge, Massachusetts and in sales offices located in major cities throughout the world. We conduct our product research and development activities primarily at our laboratory facilities in Framingham and Waltham, Massachusetts; San Antonio, Texas; and San Diego, California in the U.S.United States and at our Cambridge, U.K.United Kingdom facility. Leases for our facilities
contain typical commercial lease provisions, including renewal options, rent escalators and tenant responsibility for operating expenses. We believe that we have, or are in the process of developing or acquiring, adequate manufacturing capacity to support our requirements for the next several years.
Renal
We manufacture the majority of our supply requirements for sevelamer hydrochloride, the active ingredient in Renagel, at our facilities in Haverhill, England. We also operate a manufacturing facility in Waterford, Ireland for use in manufacturing the tablet formulation of Renagel. All of our Renagel manufacturing facilities are operational, and have received all European and U.S. approvals material to such operations. A second tablet formulation facility is under construction in Waterford to provide additional capacity and security of supply.supply, which is expected to come on line in 2008. We are currently converting one of the bulk Renagel plants in Haverhill, England to enable it to also produce Renvela which is anticipated to receive approvalbe on line in early 2008. Renvela tableting operations will be conducted in our Waterford, Ireland facility.
We contract out the manufacturing and fill-finish work for the capsule formulation of Hectorol. We are in the process of evaluating options to obtain regulatory approval and secure the supply of Hectorol filled in vials instead of ampules. In addition, we are in the process of constructing our own manufacturing capacity for filling Hectorol in vials in Ridgefield, NJ.New Jersey, which we expect will come on line in 2008.
Therapeutics
We manufacture Cerezyme, Fabrazyme and Myozyme at our multi-product manufacturing facility in Allston, Massachusetts. This facility, which we own and which contains extensive sterile filling capacity, is built on land that we hold under a 65-year lease, which expires in May 2057. We manufacture Thyrogen, Fabrazyme and Myozyme in our small-scale manufacturing facility in Framingham, Massachusetts and final drug product at our Allston facility. In addition, we fill Aldurazyme at our Allston facility. We are in the process of expanding this facility to house power generation, laboratory and administrative space to support the utilization of the facility. We are also in discussions with the FDA regarding approval of a larger-scale (2000 liter) manufacturing process for Myozyme at our Allston facility. In 2005, we commenced the design and build-out of perfusion capacity at our Geel, Belgium facility to provide back-up and expansion to our Allston bulk capacity and purification systems. In 2008, we are planning to produce the process validation lots for Myozyme at the 4000 liter scale in Geel, with approval anticipated in 2009.
At our Waterford, Ireland facility, we have installed new fill-finish capabilities for therapeutic proteins. We completed the qualification batches for the first product to be manufactured at the facility
and received approval for manufacture of the first product, Thymoglobulin, from the FDA in 2006. We are in the process of transferring and qualifying additional products with additional2006, followed by approvals for Cerezyme and Myozyme anticipated in 2007.
Transplant
We manufacture Thymoglobulin and Lymphoglobuline at a leased facility in Lyon, France, and maintain administrative offices nearby. The majorityAll of our fill-finish of Thymoglobulin is now done at our Waterford facility. We plan to shiftcompleted the remaining fill-finish work from Sanofi-Pasteur in France to our Waterford facility in 2007. We plan to complete acquisition of land in Lyon in 2007. We are in the process of permitting and design, prior to seek governmental approval to commencecommencing the construction of a new Thymoglobulin manufacturing facility with increased capacity in 2007.2008. We have experienced production issues at our current Lyon facility and have been working with the FDA to resolve those issues. Our construction of a new production facility for Thymoglobulin in Lyon is expected to support the long-term growth of this product.
Biosurgery
We produce Synvisc and other hyaluronan-based products in a manufacturing facility located in Ridgefield, New Jersey. We produce bulk hyaluronic acid and the Sepra family of products at commercial scale in our manufacturing facility in Framingham, Massachusetts.
Genetics
Our genetic and oncology testing business primarily conducts operations in clinical laboratory and administrative facilities we own in Santa Fe, New Mexico and lease in Westborough, Massachusetts; New York, New York; Tampa, Florida; Phoenix, Arizona;Arizona, Philadelphia, Pennsylvania, Vienna, Virginia; and Los Angeles, Orange, and Monrovia, California.
Oncology
We contract out the manufacturing and fill-finish work for Campath and Clolar. We are working towards establishing manufacturing capabilities for Campath to our facilities in Geel, Belgium and Waterford, Ireland.
We periodically become subject to legal proceedings and claims arising in connection with our business.
Four Through June 30, 2003, we had three outstanding series of common stock, which we referred to as tracking stocks; Genzyme General Stock (which we now refer to as Genzyme Stock), Biosurgery Stock and Molecular Oncology Stock. In 2003, four lawsuits have beenwere filed against us regarding the exchange of all of the outstanding shares of Biosurgery Stock for shares of Genzyme Stock in connection with the elimination of our tracking stocks in July 2003. Each of the lawsuits iswas a purported class action on behalf of holders of Biosurgery Stock. The first case, filed in Massachusetts Superior Court (MSC) in May 2003, alleged a breach of the implied covenant of good faith and fair dealing in our charter and a breach of our board of directors’ fiduciary duties. The plaintiff in this case sought an injunction to adjust the exchange ratio for the tracking stock exchange. The MSC dismissed the complaint in its entirety in November 2003. Upon appeal, the Massachusetts Appeals Court upheld the dismissal by the MSC of the fiduciary duty claim, but reversed the earlier decision to dismiss the implied covenant claim. The Massachusetts Supreme Judicial Court (SJC) has granted our petition for further appellate review of the Appeals Court decision reversing the dismissal of the implied covenant claim. The SJC heard oral arguments on December 4, 2006. A ruling on the appeal is anticipated in the first half of 2007. Two substantially similarThree cases were filed in the MSC in AugustMassachusetts state court, and October 2003. These cases were consolidated in January 2004, and in July 2004, the consolidatedone case was stayed pending disposition of a fourth case, which was filed in the U.S.United States District Court for the Southern District of New York, inwhich we refer to as the U.S. District Court. On June 2003. The complaint initially alleged violations of federal securities laws, common law fraud, and a breach4, 2007, the Massachusetts Supreme Judicial Court reversed an order of the merger agreement with Biomatrix, Inc., or Biomatrix, in addition toMassachusetts Appeals Court and affirmed dismissal of the first of the state law claims containedcourt actions. The remaining two state court actions remained stayed while the action filed in the other cases. The plaintiffs initially sought an adjustment toU.S. District Court progressed. In that action, the exchange ratio, the rescission of the acquisition of Biomatrix, and unspecified compensatory damages. In December 2005, the plaintiffs in this case filed an amended complaint in which they dropped all of the claims alleged in the initial complaint relating to the initial issuance of Biosurgery Stock and the acquisition of Biomatrix, and narrowed the putative class to include only those individuals who held Biosurgery Stock on May 8, 2003. We filed a motion to dismiss the amended complaint and to oppose the class certification. TheU.S. District Court had denied our motion to dismiss the successive amended complaintcomplaints and certified thisgranted plaintiffs' motion to certify a class. On August 6, 2007, we reached an agreement in principle with counsel for the plaintiff class to settle and dismiss that case for $64.0 million. The U.S. District Court entered an order approving the settlement on December 30, 2007. Because the members of the class in the New York action released all claims, the settlement and its approval, as a class action on behalf of all shareholders who held Biosurgery Stock on May 8, 2003. We filedpractical matter, resolved the two remaining actions in Massachusetts state court. Those two cases have been dismissed. As a petition asking the U.S. Court of Appealsresult, we recorded a liability for the Second Circuit to review the class certification decision, which has been denied. Discovery in this action is currently ongoing. We believe eachsettlement payment of these cases is without merit and continue to defend against them vigorously.
On March 27, 2003, the Office of Fair Trading, or OFT, in the United Kingdom issued a decision against our wholly-owned subsidiary, Genzyme Limited, finding that Genzyme Limited held a dominant position and abused that dominant position with no objective justification by pricing Cerezyme in a way that excludes other delivery/homecare service providers from the market for the supply of home delivery and homecare services to Gaucher patients being treated with Cerezyme. In conjunction with this decision, the OFT imposed a fine on Genzyme Limited and required modification to its list price for Cerezyme in the United Kingdom. Genzyme Limited appealed this decision to the Competition Appeal Tribunal. On May 6, 2003, the Tribunal issued an order that stayed the OFT’s decision, but required Genzyme Limited to provide a homecare distributor a discount of 3% per unit during the appeal process. The Tribunal issued its judgment on Genzyme Limited’s appeal on March 11, 2004, rejecting portions of the OFT’s decision and upholding others. The Tribunal found that the list price of Cerezyme should not be reduced, but that Genzyme Limited must negotiate a price for Cerezyme that will allow homecare distributors an appropriate margin. The Tribunal also reduced the fine imposed by the OFT. In response to the Tribunal’s decision, we recorded an initial liability of approximately $11 million in our 2003 financial statements and additional liabilities totaling approximately $1 million during 2004 and 2005, of which approximately $6 million were paid in 2005. Genzyme Limited and the OFT were unable to negotiate a price for Cerezyme for homecare distributors and, as a result, on September 29, 2005, the Tribunal issued a ruling establishing the discount to be provided by Genzyme Limited to homecare distributors at 7.2%, which approximates the figure used to calculate the initial liability of approximately $11 million we recorded in
2003, and the additional liabilities totaling approximately $1$64.0 million we recorded in 2004 and 2005. Genzyme Limited decided not to appeal this decision. Arising out of the OFT decision, on April 5, 2006, Genzyme Limited received a damage claim from Genzyme Limited’s former distributor, Healthcare at Home. In the fourth quarter of 2006, Genzyme Limited paid Healthcare at Home approximately $14 million, inclusive of interest and legal costs in full and final settlement of all claims, of which approximately $6 million had been previously accrued and approximately $8 million was recorded as a charge to selling, general and administrative expenses,charges, or SG&A, in our consolidated statementsstatement of operations in December 2006.
June 2007, which we subsequently paid in August 2007. We are not ablehave submitted claims to predict the outcomeour insurers for reimbursement of portions of the pending legal proceeding listed here, or otherexpenses incurred in connection with these cases; the insurer has purported to deny coverage. We intend to vigorously pursue our rights with respect to insurance coverage.
We periodically become subject to legal proceedings to whichand claims arising in connection with our business. We believe we may become subjecthave meritorious arguments in our current litigation matters and our view as of this report is that any outcome, either individually or in the normal course of business or estimate the amount or range of any reasonably possible loss we might incur if we doaggregate, is not prevail in the final, non-appealable determinations of such matters. Therefore, we have no current accruals for these potential contingencies. We cannot provide you with assurance that the legal proceedings listed here, or other legal proceedings, will not have aexpected to be material adverse impact onto our financial conditionposition or results of operations.
ITEM 4. SUBMISSION OF MATTERS TO A VOTE OF SECURITY HOLDERS
None.
Executive Officers of the Registrant
Set forth below is a list of individuals that are currently serving as our executive officers, or who served in such capacity during the fiscal year ended December 31, 2006:2007:
| Name | Age | Title | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Henri A. Termeer |
| Chairman of the Board of Directors; President and Chief Executive Officer | |||||||||||
Earl M. Collier, Jr. |
| Executive Vice President, Cardiovascular, Oncology and | |||||||||||
Zoltan A. Csimma |
| Chief Human Resources Officer; Senior Vice President | |||||||||||
Georges Gemayel, Ph.D. |
| Executive Vice President, Therapeutics | |||||||||||
Richard A. Moscicki, M.D. |
| Chief Medical Officer; Senior Vice President, Clinical, Medical and Regulatory Affairs | |||||||||||
Alan E. Smith, Ph.D. |
| Chief Scientific Officer; Senior Vice President, Research | |||||||||||
Sandford D. Smith |
| Executive Vice President; President, International Group | |||||||||||
Peter Wirth |
| Chief Legal Officer; Executive Vice President, Legal and Corporate Development; Secretary | |||||||||||
Michael S. Wyzga |
| Chief Financial and Accounting Officer; Executive Vice President, Finance |
Mr. Termeer has served as our President and a Director since October 1983, as Chief Executive Officer since December 1985 and as Chairman of the Board of Directors since May 1988. For ten years prior to joining Genzyme, Mr. Termeer worked for Baxter International Laboratories, Inc., a manufacturer of human health care products. Mr. Termeer is a director of ABIOMED, Inc. and Deputy Chairman of the Federal Reserve Bank of Boston and a trustee of Hambrecht & Quist Healthcare Investors and Hambrecht & Quist Life Sciences Investors.Boston.
Mr. Collier has served as Executive Vice President since July 1997, with responsibility for our Oncology and Cardiovascular businesses since August 2003 and our Genetics business since January 2007. He joined Genzyme in January 1997 as Senior Vice President, Health Systems, and served as Executive Vice President, Surgical Products and Health Systems from July 1997 until June 1999. He served as President of our former Genzyme Surgical Products division from June 1999 until December 2000. Mr. Collier was also responsible for our former Genzyme Tissue Repair division from December 1999 to December 2000. From December 2000 until August 2003, Mr. Collier served as President of our Genzyme Biosurgery business unit. Prior to joining us, Mr. Collier was President of Vitas
HealthCare Corporation (formerly Hospice Care Incorporated), a provider of health care services, from October 1991 until August 1995. Prior to that, Mr. Collier was a partner in the Washington, D.C. law firm of Hogan & Hartson, which he joined in 1981. Mr. Collier is a director of Encorium Group, Inc., a contract research organization which provides independent clinical trial and product development services to the pharmaceutical, biotechnology and medical devices industries. He also serves on the board of deCODE genetics, a biotechnology company that applies gene discovery to the development of drugs and diagnostics for common diseases.
Mr. Csimma has held the title Senior Vice President and Chief Human Resources Officer since March 1, 2006. He joined us in July 2000 as Senior Vice President, Human Resources. Prior to joining Genzyme, he served as Vice President, Human Resources of Wyeth Ayerst Research, a pharmaceutical research organization, from August 1998 to July 2000. During that time, Mr. Csimma also served as Site Head, Genetics Institute, for Wyeth Ayerst. From May 1988 to August 1998, he served as Vice President, Human Resources and Operations of Genetics Institute, Inc., a biotechnology company, which was integrated into Wyeth Ayerst in March 1998.
Dr. Gemayel serves as Executive Vice President with responsibility for our Renal, Therapeutics (excluding our lysosomal storage disordersLSD business unit), Transplant and Biosurgery business units. He joined us in August 2003 and served until February 2007 as Executive Vice President with responsibility for our Renal, Therapeutics (including our lysosomal storage disordersLSD business unit) and Transplant business units. For sixteen years prior to joining Genzyme, Dr. Gemayel worked for Hoffmann-LaRoche, a leading healthcare company, where he served most recently from July 2000 until August 2003 as Vice President of the United States Specialty Care unit, and from January 1998 until July 2000 as General Manager of Hoffmann-LaRoche Portugal.
Dr. Moscicki joined us in March 1992 as Medical Director, became Vice President, Medical Affairs in early 1993 and was named Vice President, Clinical, Medical and Regulatory Affairs in December 1993. In September 1996 he became Senior Vice President, Clinical, Medical and Regulatory Affairs and Chief Medical Officer. Since 1979, he has also been a physician staff member at the Massachusetts General Hospital and a faculty member at the Harvard Medical School.
Dr. Alan Smith joined us in August 1989 as Senior Vice President, Research, and became Chief Scientific Officer in September 1996. Prior to joining Genzyme, he served as Vice President—Scientific Director of Integrated Genetics, Inc., from November 1984 until its acquisition by us in August 1989. From October 1980 to October 1984, Dr. Smith was head of the Biochemistry Division of the National Institute for Medical Research, Mill Hill, London, England and from 1972 to October 1980, he was a member of the scientific staff at the Imperial Cancer Research Fund in London, England.
Mr. Sandford Smithhas held the title asof Executive Vice President since June 2006, Senior Vice President since January 2003 and President of our International Group since January 2000, with responsibility for the commercial activities for our lysosomal storage disorders,LSD, renal, transplant and biosurgery products outside of the United States, including in the Europe, Middle East, Asia PacificAsia-Pacific and Latin America regions, as well as Canada. He joined us in April 1996 and served as Vice President and General Manager of our International Group and President of our Therapeutics business. Prior to joining
Genzyme, Mr. Smith served as President and Chief Executive Officer of Repligen Corporation. Before joining Repligen Corporation, Mr. Smith also served as Vice President of Business Development and Strategic Planning for Bristol-Myers Squibb Company.
Mr. Wirth joined us in January 1996 and has served as Executive Vice President and Chief Legal Officer since September 1996 with responsibility for our corporate development and legal activities. From 2001 through October 2005, Mr. Wirth had responsibility for our drug discovery and development business. In addition, from September 1996 until June 2003, Mr. Wirth was responsible for our Oncology business.
Mr. Wyzga has served as Executive Vice President, Finance since May 2003, as Chief Accounting Officer since January 1999 and as Chief Financial Officer since July 1999. He joined us in February
1998 as Vice President and Corporate Controller and served as Senior Vice President, Corporate Controller from January 1999 until July 1999. He served as Senior Vice President, Finance from July 1999 until May 2003. From February 1997 to February 1998 Mr. Wyzga served as Chief Financial Officer of Sovereign Hill Software, Inc., a software company, and from 1991 to 1997 held various senior management positions with CACHELINK Corporation and Lotus Development Corporation. Mr. Wyzga is also director of Altus Pharmaceuticals Inc., a developer of protein therapeutics.
26
PART II
ITEM 5. MARKET FOR REGISTRANT’SREGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES
Our common stock, which we refer to as Genzyme Stock, is traded on The Nasdaq StockGlobal Select Market Inc. (“NASDAQ®”("NASDAQ®") system under the symbol “GENZ”"GENZ".
As of February 28, 2007,27, 2008, there were 3,4743,290 stockholders of record of Genzyme Stock.
The following table sets forth, for the periods indicated, the high and low sale price of Genzyme Stock as reported by NASDAQ.
|
| High |
| Low |
| ||
2006: |
|
|
|
|
| ||
First Quarter |
| $ | 75.34 |
| $ | 65.49 |
|
Second Quarter |
| 68.47 |
| 54.64 |
| ||
Third Quarter |
| 70.31 |
| 57.74 |
| ||
Fourth Quarter |
| 70.50 |
| 59.71 |
| ||
2005: |
|
|
|
|
| ||
First Quarter |
| $ | 61.40 |
| $ | 55.15 |
|
Second Quarter |
| 65.13 |
| 55.51 |
| ||
Third Quarter |
| 76.17 |
| 58.61 |
| ||
Fourth Quarter |
| 77.82 |
| 66.62 |
| ||
| | High | Low | |||||
|---|---|---|---|---|---|---|---|
| 2007: | |||||||
| First Quarter | $ | 68.77 | $ | 59.07 | |||
| Second Quarter | 67.89 | 59.79 | |||||
| Third Quarter | 66.00 | 58.71 | |||||
| Fourth Quarter | 76.90 | 62.30 | |||||
| 2006: | |||||||
| First Quarter | $ | 75.34 | $ | 65.49 | |||
| Second Quarter | 68.47 | 54.64 | |||||
| Third Quarter | 70.31 | 57.74 | |||||
| Fourth Quarter | 70.50 | 59.71 | |||||
We have never paid any cash dividends on any series of our common stock and we do not anticipate paying cash dividends in the foreseeable future.
We incorporate information regarding the securities authorized for issuance under our equity compensation plans into this section by reference from the section entitled “Equity Plans” in the proxy statement for our 2007 annual meeting of shareholders.
Issuer Purchases of Equity Securities
Stock Repurchase Program
In May 2007, our board of directors authorized a stock repurchase program to repurchase up to an aggregate maximum amount of $1.5 billion or 20,000,000 shares of our outstanding common stock over the next three years. The repurchases are being made from time to time and can be effectuated through open market purchases, privately negotiated transactions, transactions structured through investment banking institutions, or by other means, subject to management's discretion and as permitted by securities laws and other legal requirements. The manner of the purchase, the amount that we spend and the number of shares we ultimately purchase will vary based on a range of factors, including share price. The program does not obligate us to acquire any particular amount of common stock and the program may be suspended at any time at our discretion.
We did not make any purchases In 2007, we repurchased a total of 3,500,000 shares of our common stock under the repurchase plan for a total of $231.6 million of cash, including fees. The following table provides information about certain repurchases of equity securities that are registered under Section 12 of the Exchange Act during the three monthsquarter ended December 31, 2006, which is2007:
| Period | Total Number of Shares Purchased | Average Price Paid per Share | Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs | Approximate Dollar Value of Shares that May Yet Be Purchased Under the Plans or Programs | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| October 1, 2007-October 31, 2007 | 169 | (1) | $ | 70.21 | — | $ | 1,318,846,790 | ||||
| November 1, 2007-November 30, 2007 | 267,300 | $ | 72.35 | 267,300 | $ | 1,299,508,743 | |||||
| December 1, 2007-December 31, 2007 | 423,962 | $ | 73.15 | 423,962 | $ | 1,268,494,422 | |||||
| Total | 691,431 | $ | 72.84 | (3) | 691,262 | (2) | |||||
- (1)
- Represents shares from stock option exercises where employees use shares of Genzyme Stock to pay the exercise price of stock options, commonly referred to as a stock swap transaction. Shares repurchased in stock swap transactions are subsequently retired.
- (2)
- During the fourth quarter of fiscal 2007, we repurchased 691,262 shares of our common stock under the stock repurchase program for $50.4 million of net cash.
- (3)
- Represents the weighted average price paid per share for stock repurchases made during the fourth quarter of fiscal
year.2007.
The graph below compares the five-year cumulative total shareholder returns for our common stock to that of the S&P 500 Composite Index and the NASDAQ®NASDAQ® Pharmaceutical Index. The cumulative returns are based on a $100 investment on January 1, 2002,2003, with all dividends being reinvested. The comparisons shown in the graph are based upon historical data and we caution that the stock price performance shown in the graph is not indicative of, nor intended to forecast, the potential future performance of our stock. Prior to December 31, 2003, the Genzyme Stock prices used in this table reflect Genzyme General Stock before the elimination of our tracking stock structure. Information used in the graph was obtained from Standard and Poor’sPoor's and the Nasdaq Global Select Stock Market®Market®, sources we believe to be reliable, but we are not responsible for errors or omissions in such information.
Comparison of 5 Year Cumulative Total Return
ITEM 6. SELECTED FINANCIAL DATA
We incorporate our Selected Financial Data into this section by reference from the 20062007 Genzyme Corporation Annual Report under the heading “Genzyme"Genzyme Corporation and Subsidiaries—Consolidated Selected Financial Data,”" which is included in Exhibit 13 to this Annual Report.Report on Form 10-K.
ITEM 7. MANAGEMENT’S MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
We incorporate our Management’sManagement's Discussion and Analysis of Financial Condition and Results of Operations into this section by reference from the 20062007 Genzyme Corporation Annual Report under the heading “Management’s"Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries’Subsidiaries' Financial Condition and Results of Operations,”" which is included in Exhibit 13 to this Annual Report on Form 10-K.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
We incorporate our disclosure related to market risk into this section by reference from the 20062007 Genzyme Corporation Annual Report under the headings “Management’s"Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries’Subsidiaries' Financial Condition and Results of Operations—Market Risk,” “—" "—Equity Price Risk," "—Interest Rate Risk,” “—" and "—Foreign Exchange Risk” and “—Equity Price Risk,”Risk" which is included in Exhibit 13 to this Annual Report on Form 10-K.
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ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
We incorporate the financial statements filed as part of this Annual Report on Form 10-K into this section by reference from the Genzyme Corporation and Subsidiaries Consolidated Financial Statements and notes thereto included in Exhibit 13 to this Annual Report on Form 10-K.
ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE
None.
ITEM 9A. CONTROLS AND PROCEDURES
Evaluation of Disclosure Controls and Procedures
At the direction of our Chief Executive Officer and Chief Financial Officer, we evaluated our disclosure controls and procedures and internal control over financial reporting and concluded that: (1) our disclosure controls and procedures were effective as of December 31, 2006;2007; and (2) no change in internal control over financial reporting occurred during the quarter ended December 31, 20062007 that has materially affected, or is reasonably likely to materially affect, such internal control over financial reporting.
Management’sManagement's Report on Internal Control Over Financial Reporting
The full disclosure of our management’smanagement's assessment of the effectiveness of our internal controls over financial reporting as of December 31, 20062007 is set forth in the 20062007 Genzyme Corporation Annual Report under the heading “Management’s"Management's Report on Internal Controls Over Financial Reporting,”" which is included in Exhibit 13 to this Annual Report on Form 10-K.
Attestation Report of Independent Registered Public Accounting Firm
Our management’s assessment of the The effectiveness of our internal controls over financial reporting as of December 31, 20062007 has been audited by PricewaterhouseCoopers LLP, an independent registered public accounting firm. The attestation report of PricewaterhouseCoopers LLP is set forth in the 20062007 Genzyme Corporation Annual Report under the heading “Report"Report of Independent Registered Public Accounting Firm,”" which is included in Exhibit 13 to this Annual Report on Form 10-K.
None.
None.
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
We have adopted a Corporate Code of Conduct, which applies to our directors and all of our employees, including our principal executive officer, principal financial officer and accounting officer, and controller. A copy is available to you, free of charge, upon written request to the legal department at our corporate offices located at Genzyme Center, 500 Kendall Street, Cambridge, Massachusetts 02142. We intend to make all required disclosures concerning amendments to, or waivers from, this code on the governance page of our website, http://www.genzyme.com. Information contained on our website is not part of this document or the documents incorporated by reference into this document.
We incorporate information regarding our directors and executive officers into this section by reference from the section entitled “Executive"Executive Officers of the Registrant”Registrant" in Part I of this Annual Report on Form 10-K and the sections entitled “Election"Election of Directors,” “Board" "Board Meetings and Committees”Committees" and “Section"Section 16(a) Beneficial Ownership Reporting Compliance”Compliance" in the proxy statement for our 20072008 annual meeting of shareholders.
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ITEM 11. EXECUTIVE COMPENSATION
We incorporate information regarding the compensation of our directors and executive officers into this section by reference from the sections entitled “Election"Election of Directors,” “Director" "Director Compensation,” “Compensation" "Compensation Discussion and Analysis”Analysis" and related tables and narratives in the proxy statement for our 20072008 annual meeting of shareholders.
ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS
We incorporate information regarding the ownership of our securities by our directors, executive officers and 5% stockholders into this section by reference from the sections entitled “Stock Ownership”"Stock Ownership" and “Equity Plans”"Equity Plans" in the proxy statement for our 20072008 annual meeting of shareholders.
We incorporate information regarding the securities authorized for issuance under our equity compensation plans into this section by reference from the section entitled "Equity Plans" in the proxy statement for our 2008 annual meeting of shareholders.
ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE
We incorporate information regarding transactions with related parties into this section by reference from the section entitled “Certain"Certain Relationships and Related Transactions”Transactions" in the proxy statement for our 20072008 annual meeting of shareholders.
ITEM 14. PRINCIPAL ACCOUNTING FEES AND SERVICES
We incorporate information regarding our audit committee’scommittee's pre-approval policies and procedures and the fees paid to our auditors from the section entitled “Independent Auditors”"Independent Auditors" in the proxy statement for our 20072008 annual meeting of shareholders.
ITEM 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES
We are incorporating the following financial statements (and related notes) of Genzyme Corporation and Subsidiaries into this section by reference from the 20062007 Genzyme Corporation Annual Report:
| Page* | ||||||
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| F-65 | |||||
| 2005 |
| F-67 | ||||
Consolidated Balance Sheets as of December 31, |
| F-68 | ||||
Consolidated Statements of Cash Flows for the Years Ended December 31, 2007, 2006 |
| F-69 | ||||
| 2005 |
| F-71 | ||||
| F-73 |
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(a)(2).FINANCIAL STATEMENT SCHEDULES
The schedule listed below for Genzyme Corporation and Subsidiaries is filed as part of Exhibit 13 to this Annual Report on Form 10-K and is incorporated into this section by reference:
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All other schedules are omitted as the information required is inapplicable or the information is presented in the Genzyme Corporation and Subsidiaries’Subsidiaries' Consolidated Financial Statements or notes thereto.
The exhibits are listed below under Part IV, Item 15(b) of this Annual Report on Form 10-K.
All other schedules are omitted as the information required is inapplicable or the information is presented in the Genzyme Corporation and Subsidiaries’Subsidiaries' Consolidated Financial Statements or notes thereto. The exhibits are listed below under Part IV, Item 15(b) of this Annual Report on Form 10-K.
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*3.1 | Restated Articles of Organization of Genzyme, as amended. Filed as Exhibit 3.1 to | ||||
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*10.12.3 | Form of Nonstatutory Stock Option for grants under Genzyme's 2007 Director Equity Plan. Filed as Exhibit 10.3 to Genzyme's 8-K filed May 30, 2007. | |
*10.12.4 | Form of Restricted Stock Unit for grants under Genzyme's 2007 Director Equity Plan. Filed as Exhibit 10.4 to Genzyme's 8-K filed May 30, 2007. | |
*10.13 | 2001 Equity Incentive Plan, as amended. Filed | |
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*10.15 | 1999 Employee Stock Purchase Plan, as amended. Filed as Exhibit | |
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*10.23 | Supply Agreement, dated January 24, 2006, by and between Cambrex Charles City, Inc. and Genzyme. Filed as Exhibit 10.1 to | |
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*10.27.1 |
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*10.27.2 | Amended and Restated Contract Purchase and Supply Agreement between Invitrogen Corporation and Genzyme Corporation effective December 31, 2007. Filed as Exhibit 10.1 to Genzyme's Form 10-Q for the quarter ended September 30, 2007.** | |
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EXECUTIVE COMPENSATION PLANS AND ARRANGEMENTS
Exhibits 10.1310.11 through 10.22.110.21.1 above are management contracts or compensatory plans or arrangements in which our executive officers or directors participate.
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Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| GENZYME CORPORATION | |||
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| /s/ MICHAEL S. WYZGA |
Michael S. Wyzga Executive Vice President, Finance, Chief Financial Officer, and Chief Accounting Officer | |||
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the Registrant and in the capacities and on the date indicated.
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/s/ HENRI A. TERMEER Henri A. Termeer | Director and Principal Executive Officer |
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Michael S. Wyzga |
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Richard F. Syron | Director | February 29, 2008 | |||||||||||||
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