Akshay K. Vaishnaw
Thanks, everyone. John, good and afternoon,
continue making EMA, approval. is this both with the available medicine process, FDA which hereditary of goal treatment as and patisiran, by the development as with ATTR quickly of patients we the with amyloidosis. to for through patisiran under collaboratively review upon currently agencies begin Patisiran work is the Let's review to possible in and regulatory
clinical or months presented XX study. Furthermore, in Patisiran in from of study have patisiran investigational As potential primary these of profile. the only new in aspects patients patisiran you In baseline. week we with manifestations patients manifestations to date, potential regard, amyloidosis Phase the and in to mNIS+X is study know, analysis to mortality data and at with treatment demonstrated continue safety. of gather hATTR patisiran's of the APOLLO demonstrated The pivotal endpoint post-hoc all-cause the and the hospitalization in conducted the to of patients just events and is over approved patisiran safety last describe mortality. the new to amyloidosis of X diverse AAN analyze majority Norfolk-QOL negative the the hospitalization In efficacy was a impact fall, compared pleased hATTR XX rate we the last associated patisiran. results APOLLO months. this endpoint and hospitalization the a mortality. APOLLO, were APOLLO in improvement improve present with an data on encouraging largest therapy a majority and depicts on disease the Conference key from we to composite depicted figures secondary In looking data, left figure change slide X, and the at of of to on
has can all-cause strengthen ATTR right, composite XX% an rate patisiran-treated believe – these rate for patients approximately data see, transformative in all-cause We of hospitalization over hereditary the the this and in patients to an hospitalization patients was evidence reduction placebo. of and figure observed there As with XX% of relative to in treatment mortality on in approximately XX the Similarly, a we demonstrating the decrease existing you potential to cardiac months placebo. body the forms if all post-hoc patisiran-treated that be relative amyloidosis. approved, patisiran, in
of to overall, the deaths study, none of as to may to tolerability considered reported adverse and moderate frequently The there was most were deaths as were were mild in events the lower recall, were discontinuation peripheral with compared These patients XX and the the study Adverse events in patisiran infusion-related in that occurred leading you commonly frequency As in generally severity. patisiran group to APOLLO patisiran-treated placebo. regard treatment related were lower to to in and reactions. edema placebo. safety which group drug; compared more
August as amyloidosis effect levels positive in where gait data a strain, echocardiographic treatment Furthermore, conjunction assessment. cardiac multiple functional with . included an a appear EU also NT-proBNP, seeks subpopulation, on the involvement. being left neurologic mid-XXXX the benefits We late approval believe cardiomyopathy with effects improvements and associated patients benefits and measures biomarker, of as to with ventricular We of Meeting These and parameters, improvements, for an results for application potential approval XXXX including March. thickness left associated we're the of across that patisiran with U.S., in well ISA indicator at XX in significant with cardiac stress presented additional expedited These a PDUFA also under was reviewed ventricular a of patisiran is an the from status. the with in cardiac highlighting on speed, favorable wall demonstrated improvements on date range our for improvement, be important in hATTR recently track
We also the in plan rest year. in J-NDA regulatory world additional in a of countries in packages mid-XXXX, as later well submit as to Japan the other
X is levels advance of to RNAi subcutaneous the with of we're patisiran the XX a single study comparable milligrams investigational robust study. platform In ATTR us Phase expect to uses as our no low XXX demonstrated supported days late we ALN-TTRscXX knockdown guidance, addition an due observed amyloidosis. conjugate to in for injection with a doses well-tolerated, TTR generally ESC-GalNAc ALN-TTRscXX Consistent allows previous AEs. technology pivotal ALN-TTRscXX therapeutic XXXX. into with given of study, over for comprehensive dose to developing achieve APOLLO Phase or was once-quarterly ALN-TTRscXX as SAEs a discontinuations ALN-TTRscXX patisiran, in subcutaneous TTR for potential those also knockdown a X program to our administration. and and maintained In and
believe of very FDA possible. amyloidosis subcutaneously endpoint patients with to as trial an population, would bringing in as study rapidly alignment, support attractive as administered and ALN-TTRscXX treatment an While that a EMA are our option designs approval we final a TTR the knockdown pending hATTR
complete a including setting ATTR Regarding in considering disease. result head-to-head study need opportunity, we'll cardiomyopathy ATTR the from now to the tafamidis for comparing we're But potential tafamidis ATTR-ACT later see ALN-TTRscXX wild-type with study year. the Pfizer's this wild-type the of with
givosiran turn recent we've program, where made in now significant to months. also Let's our progress
patients from Phase givosiran the for presented the part porphobilinogen and X both four-dose minor for responsible know, and X rolled primary reductions well reductions The XX% rate the last of the another mean in to part annualized have disease relative as cohorts trial, transitioned development vast level into of for the all the of OLE. month, as PBG, givosiran for givosiran complete acid in or from in disease C treatment porphyrias. placebo. early over hemin up activity the expanded acute the in With to XX data Moreover, majority was neurotoxic is At of resulted led administration given data received dosing, from annualized in study, consumption XX of further of the you Phase X X now months. with about or the to OLE attack clinical we In administration treatment of the the in as study. ongoing Part the X and study intermediate improvement patients of Phase As givosiran manifestations, from month, mean X/X ALA, duration biomarker. treatment evidence of Phase into there XX% EASL the hepatic
period Specifically, suggesting X symptoms. mean treatment attack use hemin further in reductions those givosiran the AAR hemin to dosing use hemin Phase exceeded in observed for can These continued of XX%, use generate to and X, and and recorded period. of during relative rate these amelioration we XX% annualized AAR that observed even in reductions the Phase run-in the
reassurance OLE In related givosiran oral terms after patients asthma, as assessed study had be IgE, detected two with reaction possibly patients seen have history is with to X,XXX SAEs, reactions definitely givosiran. did we study, study The represents that Notably, conjugate the were SAE patient management report six continue drug. allergy anaphylactic and this with no Furthermore, the antibodies, patient acne dosed an medical event. cream subsequently in past to with serious presented related patient anaphylactic third and over to from Phase of the siRNAs this latex adverse an in study. occurred gloves. us patient. assessed the patients had resolved our X event case of isolated that the none including safety, GalNAc In one across who dose entire allergic this anti-drug an syndrome, giving The and had receiving the to a of a in of only reaction of events in pipeline, there
which These We in analysis in the patients three year X the comprise total we've also efforts MAA dosing. announced analysis medicine from is bring wait of file to we analysis positive. ALA based givosiran. result reasonably positive months earnings an interim endpoint of and to XX market believe report that acceleration in forward and regarding the position conditional This the then today interim authorization On clinical is to they first of we've full in the enrolled accelerated as (XX:XX) approval end ENVISION's also givosiran. XXXX the assuming path regulators NDA the in lead our trial will is us earnings for patients XXXX, release ENVISION be of in reductions our predict results with likely forward promising the an study to results a marketing urine in Phase when reach that with will for results regulatory around surrogate that under at/or submit positive significant investigational path in our a interim interim path we'll the to considerations accelerated an patients. upon support, forward best for If study pathway, a levels evaluate the the European had benefit. that full this We've announced then release an pending in discussions access Europe with representing some they're to
Let's progress development is the hyperoxaluria treatment or type for primary X turn of lumasiran, now to which of recent PHX. in
our and We of pleased oxidase, recently production liver-kidney PHX. damage substrate ultra-rare we've a rights and are which stones transplant. for kidney to in disease an PHX glycolate oxalate Treatment depleting enzyme announce the efficacy Sanofi dual with with directly over were now the involve retained additional will the kidney, often and into the typically and report We've in study to painful completed Based we were lumasiran build other options which thereby which OLE and the crystals to study up Designation safety the to roll enrollment the X/X and targets beginning necessary to contributes following for to As the Phase long-term Breakthrough on promising lumasiran PHX lumasiran's year later opt-in to patients. pleased reminder, children chronic decision this in its tissues. a is evaluate patients, of in X/X Phase EU. in XX oxalate, results PHX dialysis by now Lumasiran limited, expect in recurrent Phase PRIME the and and global decline U.S. pathophysiology commercialization. the that receive leading of kidney orphan primarily and very in development of X/X data, clinical designation the we the patients
we reached for the FDA alignment morning, of design this our Just pivotal on with trial the announced that lumasiran. our we've
late guidance XXXX. report approximately we in our trial a oxalate Phase a Based top XXXX, urinary based of in primary the results pivotal this start study and the have this than trial mid-XXXX, sample size at of endpoint line reduction months. X expect six earlier Specifically, to will of will have from on previous XX study The design, patients. on now to
a efforts we in Assuming NDA significant which in to an to results, expect bring medicine this to acceleration position positive to XXXX, investigational in patients. submit a represents early our be
Let's our begin of program, with development rare fitusiran program, turn treatment to (XX:XX) I'll briefly disorders. which for our bleeding the is hemophilia and and in
were first our the OLE pleased, in at X X is Our to Phase and partners initiate Sanofi, dosing Phase together running we in and the back program. quarter, up study with ATLAS
X,XXX enrolled inclisiran the the XX and Medicines having been by XX impressed partner, execution studies the ORION-X, treatment to Company, of we've Turning for very with patients. our hypercholesterolemia, The fully with
from seeing X Hereto, the in topline Phase program look to XXXX. we results forward
we GalNAc-siRNA so going comprised and conjugate larger further updates to which forward have look forward, safety studies database safety for far encouraging. a been these Importantly,
another expected studies As in trial, and of which safety now, Company of inclisiran planning conduct us mid-XXXX. years the patient cardiovascular Medicines X,XXX a patients ORION-X, also XX,XXX exposure have years adds is begin outcomes and provided with over of enroll data. day is every The to to five
with at or and track wave programs. on ESC+ ALN-HBVXX we Manmeet? In excited liver are XXXX of now program our regulatory of turn We've I'll review financial with with and With programs. also now new multiple clinical our goal, a quarter first results. in review guided programs four in summary, advancement also deficiency-associated and achieve Manmeet our exciting that, we and partner, stage recent includes platform to ALN-AATXX to our our had Vir. we're programs CTN about period Phase which having a XXXX, in it next pipeline very with over to least under to the Alpha-X disease, advanced the Finally, this of one earlier for X exceed antitrypsin one beginning have