Patisiran Meets Primary Endpoint in APOLLO-B Trial

The phase 3 APOLLO-B study examining use patisiran (ONPATTRO) in patients with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy has met both its primary and first secondary, according to a release from Alnylam Pharmaceuticals.

Announced on August 3, the company announced the trial had met its primary endpoint of a statistically significant improvement in 6-minute walk test at 12 months with patisiran compared to placebo therapy and its first secondary endpoint of providing a statistically significant improvement in quality of life at 12 months with patisiran compared to placebo. In their release, the company also noted plans to use data from the study in a supplemental new drug application with the US Food and Drug Administration (FDA) in late 2022.

“We are thrilled that APOLLO-B successfully met all its major objectives, which we believe for the first time validates the hypothesis that TTR silencing by an RNAi therapeutic can be an effective approach for treating the cardiomyopathy of ATTR amyloidosis,” said Pushkal Garg, MD, Chief Medical Officer of Alnylam, in the aforementioned release. “ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure, affecting greater than 250,000 patients around the world. These patients have limited treatment options, and disease progression is common. As such, we are encouraged to see the potential of patisiran to improve the functional capacity and quality of life of patients living with this fatal, multi-system disease.”

A phase 3, randomized, double-blind, placebo-controlled trial APOLLO-B was launched in 2019 and conducted at 69 sites in 21 countries with the intent of assessing the efficacy and safety of patisiran in patients with ATTR amyloidosis with cardiomyopathy. The trial enrolled 360 adult patients and randomized them in a 1:1 ratio to receive either 03.mg/kg patisiran or placebo intravenously every 3 weeks over a 12-month double-blind treatment period. At the conclusion of this 12-month period, study protocol requires patients to be switched to patisiran for an open-label extension period.

The primary endpoint of the trial was change in from 6-minute walking test score from baseline to 12 months compared to placebo therapy. Secondary endpoints for the trial included health-related quality of life, which was measured through KCCQ change, and a trio of composite outcomes. These composite outcomes included a composite of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-minute walking test score, a composite of all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline, and a composite of all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in the overall study population.

Later in their release, Alnylam Pharmaceuticals highlighted the safety profile of patisiran observed in double-blind treatment period of the trial, including similar frequencies of adverse events (91.2% and 94.4%, respectively) and serious adverse events (33.7% and 35.4%, respectively) among the patisiran and placebo arms of the trial.

“I am delighted by the results of the APOLLO-B study, which suggest the potential for patisiran to be a treatment option for patients with ATTR amyloidosis with cardiomyopathy, assuming favorable regulatory review. In addition, the APOLLO-B data further strengthen our confidence in our Phase 3 HELIOS-B study of vutrisiran in ATTR amyloidosis with cardiomyopathy, which is expected to report out in early 2024,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam, in the aforementioned release.

Alnylam Pharmaceuticals noted plans to presented full results of the APOLLO-B study as part of a late-breaking session at the 18th International Symposium on Amyloidosis on September 8, 2022, in Germany. Patisiran is currently approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults and is also approved in the European Union, Switzerland, and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy.