- In a slide presentation released today, Alnylam (ALNY -1.1%) detailed the results from its investigation into the imbalance of deaths in the Phase 3 ENDEAVOR study assessing RNAi therapeutic revusiran in patients with hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM). The company terminated development for the indication 10 months ago after a safety review revealed a 16:2 imbalance in mortality compared to placebo.
- The number of all-cause deaths in the study in the revusiran and placebo arms was 18 and 2, respectively. The number of CV-related deaths was 16 and 2, respectively (slide #16).
- The investigation focused on four hypotheses (slide #38) to account for the imbalance, but none proved to be the smoking gun.
- Hypothesis #1: Mortality related to a baseline imbalance. The baseline characteristics were generally balanced although there were more patients at least 75 years old in the revusiran arm.
- Hypothesis #2: Mortality resulted from cardiotoxicity of revusiran. No clinical evidence found.
- Hypothesis #3: Mortality resulted from pharmacokinetics/pharmacodynamics of revusiran. No evidence found.
- Hypothesis #4: Mortality imbalance from lower-than-expected mortality in placebo arm. Some evidence found.
- The company says the data will inform the appropriate design of subsequent studies. A Phase 3 study, APOLLO, assessing patisiran in hATTR patients with polyneuropathy is ongoing.
- Previously: Alnylam bags revusiran development; shares plummet 43% after hours (Oct. 5, 2016)
- Now read: Alnylam Pharmaceuticals (ALNY) & Sanofi (PA:SASY) Genzyme Report Positive Results from Ongoing Phase 2 Open-Label Extension Study - Presentation
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