Alnylam’s Patisiran Clears Phase III Hurdle in ATTR With Cardiomyopathy

Alnylam CEO Yvonne Greenstreet_Alnylam

Alnylam CEO Yvonne Greenstreet_Alnylam Pharmaceuticals

Alnylam Pharmaceuticals announced results Thursday from the APOLLO-B study of patisiran that showed improved functional capacity in transthyretin-mediated (ATTR) amyloidosis patients with cardiomyopathy.

After 12 months of treatment, scores on the 6-Meter Walk Test (6-MWT) improved by nearly 15 meters more in the patisiran group, as compared with placebo (p=0.0162). Patisiran also significantly improved health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary ( KCCQ-OS). 

These recent data from APOLLO-B were presented Thursday in a late-breaker session at the 8th International Symposium on Amyloidosis (ISA).

Enrolling 360 ATTR patients with cardiomyopathy, APOLLO-B is a Phase III, randomized and double-blinded global study that compared Patisiran against placebo. The active intervention was given as a 0.3-mg/kg intravenous dose, delivered once every three weeks over 12 months.

APOLLO-B’s primary outcome is functional capacity measured by the 6-MWT. The first secondary endpoint assessed meaningful benefit on health status and quality of life based on the KCCQ-OS. Secondary composite endpoints were frequency of cardiovascular events and 12-month change in 6-MWT. Patisiran failed to meet the composite measure of all-cause mortality, thus the other secondary measures were not measured. 

In terms of blood biomarkers, patients treated with patisiran saw an 87% drop in transthyretin concentration after 12 months. The exploratory endpoint of NT-proBNP levels, an indicator of cardiac stress, was also significantly improved in the patirisan arm.

Patisiran also demonstrated an encouraging safety and tolerability profile, inducing no worrying cardiac safety signals over the treatment period. 

The totality of the results not only paint a robust clinical profile of patisiran for ATTR with cardiomyopathy but also confirms the company’s RNA-interference approach to lowering transthyretin levels, Pushkal Garg, M.D., CMO at Alnylam said. 

Alnylam intends to file a supplemental new drug application for patisiran in this indication later this year.

The company also presented findings from a Phase II open-label extension study in ATTR patients with polyneuropathy. Over 36 months of follow-up, patients who initiated patisiran treatment earlier saw better survival and motor outcomes than placebo comparators, Alnylam reported.

Caused by the build-up of transthyretin-amyloid fibrils in tissues and organs across the body, ATTR is a rare and progressive disorder that often leads to motor problems and organ dysfunction. There is currently no cure for ATTR.

Patisiran is an RNA interference therapeutic that helps manage ATTR by binding to the transthyretin messenger RNA, preventing it from producing the culprit protein.

In the United States and Canada, patirisan is approved under the brand name Onpattro for the treatment of polyneuropathy in adult patients with hereditary ATTR. The drug has also been given regulatory nods in the European Union, Switzerland, Brazil and Japan.

Back to news