- Alnylam Pharmaceuticals said Wednesday it stopped development of revusiran, its experimental drug for hereditary ATTR amyloidosis with cardiomyopathy, citing safety concerns after a review found more patients died in the treatment arm than those on placebo.
- While development for the revusiran program was discontinued, Alnylam said the decision would not affect its other Phase 3 study investigating patisiran in hATTR amyloidosis with polyneuropathy.
- The announcement caused shares in Alnylam to plummet in value, dropping by more than 45% in Thursday morning trading.
Alnylam said it decided to discontinue revusiran development after reports of new onset or worsening peripheral neuropathy in the company's Phase 2 OLE study. Those reports prompted the company to request a review from the data monitoring committee (DMC) for revusiran's Phase 3 ENDEAVOUR study.
While the DMC didn't find evidence of drug-related neuropathy, it recommended halting the trial. Alnylam then reviewed unblinded data from the trial and found "an imbalance of mortality in the revusiran arm as compared to placebo."
Alnylam CEO John Maraganore, speaking on a call with analysts Wednesday evening, said that 18 deaths were reported, out of 206 patients in the study.
"While this outcome is disappointing given the lack of available treatment options for patients suffering from this devastating disease, we remain committed to serving the needs of the ATTR amyloidosis community," said Maraganore. He noted the company’s continued effort to develop other drugs in its pipeline.
Still, Alnylam is perplexed about what went wrong. "There is no current explanation for the cause of these findings, and we don’t have all the answers that we would like to have," the CEO said.
ATTR amyloidosis is a progressively debilitating and often fatal disease caused by deposition of transthyretin in peripheral tissues. Hereditary ATTR amyloidosis with cardiomyopathy impacts about 40,000 people worldwide, according to the company.
The revusiran setback may have long-term consequences. "Longer follow-up would be needed to rule out similar safety concerns for the technology platform, (the revusiran) setback might be program/disease specific as suggested by our analysis," said analyst Gena Wang of Jefferies. She pointed to high risk for the company’s TTRsc02 development, another ATTR amyloidosis in Phase 1, "given seemingly lack of efficacy with revusiran."
Last week, Alnylam said it halted continuation of its proposed liver disease drug ALN-AA based on safety concerns in a Phase 1/2 study and will move to another compound that is currently in preclinical testing.
The company said the revusiran decision does not affect eight other RNAi programs in development. That includes patisiran, currently in Phase 3, which is focused on treatment of hATTR amyloidosis with polyneuropathy.