Positive topline results were announced from a phase 3 study evaluating the efficacy and safety of patisiran in adults with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

The multicenter, randomized, double-blind, placebo-controlled APOLLO-B study (ClinicalTrials.gov Identifier: NCT03997383) included 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Patients were randomly assigned 1:1 to receive patisiran 0.3mg/kg or placebo intravenously every 3 weeks for 12 months.

Findings showed that treatment with patisiran met the primary endpoint resulting in a statistically significant improvement from baseline in the 6 Minute Walk Test (6MWT) at 12 months vs placebo (P =.0162). Additionally, a statistically significant improvement in health-related quality of life (secondary endpoint; measured by the Kansas City Cardiomyopathy Questionnaire) was observed in the patisiran arm when compared with placebo (P =.0397).

With regard to the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, the Company reported a nonsignificant result (P =.0574). As such, formal statistical testing was not performed on 2 composite endpoints, which included all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits.  

The most frequently observed adverse events included infusion-related reactions, arthralgia, and muscle spasms. There were 4 deaths (2.2%) reported in the patisiran arm and 10 deaths (5.6%) in the placebo arm, according to an all-cause mortality efficacy analysis.

Full study results will be presented at the 18th International Symposium on Amyloidosis on September 8, 2022, in Heidelberg, Germany. The Company plans to submit a supplemental New Drug Application for patisiran to the Food and Drug Administration 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. 

Patisiran, a transthyretin-directed small interfering RNA, is currently marked under the brand name Onpattro for the treatment of polyneuropathy of hereditary ATTR amyloidosis in adults.


Alnylam reports positive topline results from APOLLO-B phase 3 study of patisiran in patients with ATTR amyloidosis with cardiomyopathy. News release. Alnylam Pharmaceuticals, Inc. Accessed August 3, 2022. https://www.businesswire.com/news/home/20220803005528/en/Alnylam-Reports-Positive-Topline-Results-from-APOLLO-B-Phase-3-Study-of-Patisiran-in-Patients-with-ATTR-Amyloidosis-with-Cardiomyopathy