Alnylam drops revusiran development on risk-benefit issues

US RNAi therapeutics company Alnylam Pharmaceuticals (Nasdaq: ALNY) has decided to halt dosing in the ENDEAVOUR Phase III study on the recommendation of the Data Monitoring Committee (DMC).

As a result, the company will discontinue development of revusiran, an investigational RNA interference (RNAi) therapeutic that was being studied for the treatment of hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM). Alnylam’s shares plunged 43% to $40.75 in after-hours trading on Wednesday following the announcement.

Following recent reports in the Phase II OLE study of new onset or worsening peripheral neuropathy, the ENDEAVOUR DMC assembled at the company’s request to review these reports and ENDEAVOUR data on an unblinded basis. The DMC did not find conclusive evidence for a drug-related neuropathy signal in the ENDEAVOUR trial, but informed the company that the benefit-risk profile for revusiran no longer supported continued dosing. The company subsequently reviewed unblinded ENDEAVOUR data which revealed an imbalance of mortality in the revusiran arm as compared to placebo.