EXHIBIT 99.3
Contact:
Investors: Media:
Ann Tanabe Daniel Budwick
Director, Investor Relations BMC Communications
and Corporate Communications (212) 477-9007 ext. 14
Encysive Pharmaceuticals
(713) 796-8822
Hershel Berry
The Trout Group
(415) 392-3385
FOR IMMEDIATE RELEASE
THELIN(TM) MAY OFFER ALTERNATIVE FOR PAH PATIENTS WHO HAVE FAILED ON BOSENTAN,
ACCORDING TO DATA PRESENTED AT EUROPEAN RESPIRATORY SOCIETY CONGRESS
Study Shows Liver Toxicities Experienced by Patients on Bosentan
Were Not Experienced on Thelin
HOUSTON- SEPTEMBER 8, 2004- Encysive Pharmaceuticals (Nasdaq: ENCY) today
announced the presentation of new clinical data on Thelin(TM) (sitaxsentan) in
pulmonary arterial hypertension (PAH), at the European Respiratory Society (ERS)
14th Annual Congress (September 4-8, 2004) in Scotland. Data from this single
center experience suggests that Thelin may offer an alternative for PAH patients
whose conditions are worsening on bosentan. Two other abstracts were presented
at the ERS meeting on Thelin.
Data from this first study was presented by clinical investigator Adaani Frost,
M.D., Baylor College of Medicine, Houston, Texas. Entitled, "Sitaxsentan Sodium
for the Treatment of Pulmonary Arterial Hypertension in Patients Failing
Bosentan: Preliminary Single Center Data," the trial showed that 10 out of 11
PAH patients who had failed on bosentan due to clinical deterioration or liver
toxicities improved or stabilized when given Thelin oral therapy. All 10
patients are continuing on Thelin today, some as long as 10 months.
Eight (8) patients in the study who had deteriorated on bosentan were given
Thelin 100 mg and followed for up to 12 weeks. Seven patients stabilized or
experienced improvement in the six-minute walk test (6MW), a standard
measurement of function in patients with PAH. One patient in the study
discontinued Thelin treatment due to continued disease progression and had no
evaluable 6MW measurements. Three other patients were enrolled after failing
bosentan therapy due to liver toxicity. All three improved clinically on Thelin
without recurrence of their liver abnormalities. One patient who had clinically
deteriorated on bosentan experienced a single occurrence of an abnormal liver
function test. This patient has continued on Thelin without a recurrence.
"As the first generation, nonselective endothelin receptor antagonist, bosentan
has provided an important treatment option for patients with PAH. We do,
however, see up
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to one-third of patients come off this therapy due to lack of efficacy or liver
toxicities," said Dr. Frost. "While trials are ongoing, sitaxsentan, an oral ETA
selective endothelin receptor antagonist, may provide value to newly diagnosed
PAH patients. The exciting potential from this study, however, is the
opportunity for sitaxsentan to salvage some of the one-third of patients who are
currently failing bosentan therapy."
"The clinical strategy for Thelin is to expose a broad and multi-faceted patient
group to our selective endothelin antagonist," said Terrance Coyne, M.D., Vice
President and Chief Medical Officer of Encysive Pharmaceuticals. "In addition to
alternatives for de novo patients, one of the greatest and most immediate needs
in PAH today is the development of effective alternative treatments for those
failing on current options. We believe Thelin, with its selective mode of
action, has the potential to be an important new option for these
difficult-to-treat patients."
ADDITIONAL DATA PRESENTATIONS
The second abstract, entitled, "Long-Term Sitaxsentan Therapy in PAH," Drs.
Horn, Langleben, et al., demonstrated that Thelin was similarly effective in
improving symptoms at doses of 100 mg and 300 mg. Given the better safety
profile for the 100 mg dose, the data supports the selection of 100 mg as the
maximum dose.
The third abstract, entitled, "Efficacy of Sitaxsentan, an Endothelin-A Receptor
Antagonist in PAH in Traditional Versus Expanded Study Populations," by Drs.
Frost, Langleben et al., was also presented at the meeting. The data supports
the existence of a "ceiling effect" as provided for in traditional PAH trial
designs. Frequent exclusion of patients with milder PAH, in order to increase
treatment effect sizes and statistical power, is customary when using 6MW as the
endpoint. STRIDE-1, a 12-week, randomized, double-blind, 178-patient trial
employing placebo and Thelin at 100 mg or 300 mg doses, included patients with
NYHA functional class II, congenital heart disease and a baseline 6MW >
450m-groups often excluded from previous trials. For patients meeting
traditional enrollment criteria (NYHA class III or IV and 6MW = 450m at baseline
with idiopathic PAH or PAH-related to connective tissue disease), Thelin
produced a robust increase in 6MW of 65 meters (p=0.0002) vs. 34 meters
(p=0.0005) in the intent-to-treat patient group.
ABOUT THELIN AND PAH
Thelin is a small molecule that blocks the action of endothelin, a potent
mediator of blood vessel constriction and growth of smooth muscle in vascular
walls. Endothelin receptor antagonists may prove to be effective in the
treatment of a variety of diseases where the regulation of vascular constriction
is important. Thelin is 6,500-fold selective in the targeting of the endothelin
A receptor.
Pulmonary arterial hypertension (PAH) is a condition that involves high blood
pressure and structural changes in the walls of the pulmonary arteries, which
are the blood vessels that connect the right side of the heart to the lungs. PAH
causes shortness of breath, limits activity, and is eventually fatal unless
treated successfully with heart and lung
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transplants. Primary and secondary PAH are estimated to afflict approximately
80,000 to 100,000 people worldwide, many of whom are children and young women.
Side effects of Thelin seen in the program to date, and which occurred more
frequently than in placebo, include liver dysfunction (increased ALT and AST),
headache, edema, constipation, nasal congestion and flushing. Because Thelin
inhibits the metabolism of warfarin, the dose of warfarin should be adjusted
downward when co-administered with Thelin.
ABOUT ENCYSIVE PHARMACEUTICALS
Encysive Pharmaceuticals Inc., a biopharmaceutical company focused on the
discovery, development and commercialization of novel drugs, is recognized for
our expertise in small molecule drug development and vascular biology.
Argatroban, our first FDA-approved product, is being marketed by GlaxoSmithKline
for heparin-induced thrombocytopenia. Encysive Pharmaceuticals is in Phase III
development of the endothelin antagonist, Thelin, for pulmonary arterial
hypertension. Our majority-owned affiliate, Revotar Biopharmaceuticals AG, is in
Phase II development with the selectin antagonist bimosiamose in asthma,
psoriasis and atopic dermatitis. Encysive Pharmaceuticals has several other
research and development programs ongoing for a range of cardiovascular and
inflammatory diseases. To learn more about Encysive Pharmaceuticals please visit
our web site: www.encysive.com.
This press release contains "forward-looking statements" within the meaning of
Section 27A of the Securities Act of 1933, as amended, and Section 21E of the
Securities Exchange Act of 1934, as amended. These forward-looking statements
are subject to certain risks, trends and uncertainties that could cause actual
results to differ materially from those projected. Among those risks, trends and
uncertainties are timing and cost of our clinical trials, attainment of research
and clinical goals and milestones of product candidates, attainment of required
government approvals, sales levels of our products and availability of financing
and revenues sufficient to fund development of product candidates and
operations. In particular, careful consideration should be given to cautionary
statements made in the various reports Encysive Pharmaceuticals, including as
Texas Biotechnology Corporation, has filed with the Securities and Exchange
Commission. The Company undertakes no duty to update or revise these
forward-looking statements.
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