Alnylam Adjusts ATTR Trial Goals for Amvuttra

Alnylam Pharmaceuticals is making significant changes to the goals of its Phase III clinical trial for Amvuttra, a novel RNA interference therapy designed for patients with ATTR amyloidosis who also suffer from cardiomyopathy. The company revealed these adjustments during its recent financial report.

The HELIOS-B study, which is focused on the effects of vutrisiran in the specified patient group, will see "updates" to both its primary and secondary goals. Alnylam is now projecting to release the main findings in mid-2024, around June or July.

An analyst from Mizuho Securities, Salim Syed, shared his thoughts in a communication to investors, suggesting that the alterations to the trial's statistical plan may be a response to insights gained from a prior study. He pointed out that it is unusual for a company to change its statistical approach unless it feels it is necessary to do so.

The revised plan entails an additional three months of observation, extending the study period to 33 months. As part of the announcement, Alnylam will also review long-term data from its APOLLO-B study.

Syed speculated that the extension could be an indication that the event rates in the HELIOS-B study were not meeting the company's expectations at the 30-month mark. He also highlighted a change in the way the primary endpoint will be assessed, which now includes an analysis of all patients and specifically those receiving monotherapy.

Although no further details were provided, Amvuttra continues to be an important asset in Alnylam's development pipeline. The drug gained approval in 2022 for the treatment of transthyretin-mediated (hATTR) amyloidosis in adults.

Alnylam also shared some insights from the APOLLO-B study, which evaluated patisiran as a treatment for cardiomyopathy associated with ATTR. The drug successfully achieved its primary endpoint by slowing the decline in the six-minute walk distance at 12 months in comparison to a placebo and also showed improvements in secondary endpoints.

However, the FDA did not approve the label extension for patisiran, stating that Alnylam had not provided sufficient evidence of the therapy's benefits for the indication.

Pushkal Garg, Alnylam's Chief Medical Officer, stated during the earnings call that the company will concentrate on submitting a supplemental New Drug Application (sNDA) for vutrisiran in other regions, contingent on positive results from the ongoing HELIOS-B study. He reminded that HELIOS-B is studying a similar population to APOLLO-B but with a primary outcomes endpoint focused on all-cause mortality and recurrent cardiovascular events.