The FDA attacked Alnylam in an untitled letter regarding Amvuttra’s consumer website, accusing the biotech company of presenting misleading open-label data about the drug’s effectiveness.
A page on the website about how Amvuttra may help patients with transthyretin amyloid cardiomyopathy includes data from Helios-B, a phase 3 trial conducted by Alnylam to evaluate RNAi therapy. This trial compared Amvuttra to a placebo. After a three-year double-blind study period, Alnylam conducted an open-label extension study in which all participants, including those in the placebo group, were allowed to take Amvuttra.
The website includes data from the double-blind period, as well as analyzes conducted 6 months after the open-label expansion. The FDA’s issues with the website relate to claims supported by open-label analyses, including the statement that over 3.5 years Ambutra had a 36% lower risk of death than a placebo.
The FDA said there was no true placebo control group left after 3 1/2 years because patients were not blinded and were switched to Amvuttra. The FDA said the open-label nature of the trial introduced bias and confounding, and the lack of concurrent controls meant it was unclear whether Amvuttra or other factors were driving the results after the double-blind period.
Alnylam’s website includes a warning that this analysis was not part of the original plan and that other factors may have influenced the results. However, although the FDA heeded this warning, it concluded that the claim was still misleading because an open-label extension study failed to support the conclusion.
The FDA said this misleading claim misbrands Amvuttra and that distribution of the drug is a violation of the Federal Food, Drug, and Cosmetic Act. In a letter sent on April 23, the agency asked Alnylam to take immediate action and gave the biotech company 15 business days to respond. As of May 7, the website still contained claims that the FDA disputed.
Since the FDA began cracking down on direct-to-consumer sales last year, Alnylam has received two untitled letters. The FDA sent its first letter (PDF) in September in response to Amvuttra’s television ads. The FDA said the advertisement misleadingly suggested that “patients treated with Ambtra do not need to worry about the effects of cardiomyopathy.” The agency said Alnylam lacks test data to support that impression.
The FDA shut down the first untitled letter in November after concluding that Alnylam had addressed its concerns (PDF). The agency issued termination notices for most of the untitled letters it sent during its initial flurry of activity in early September. An untitled letter from that batch with no termination notice includes correspondence the agency sent to Alexion, Amgen, Novartis and UCB.
