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BREAKING NEWS: The U.S. Food and Drug Administration has issued a complete response letter for Alnylam Pharmaceuticals’ Patisiran, an investigational RNAi therapeutic for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis.

This letter denies approval for the treatment of cardiomyopathy of ATTR amyloidosis with patisiran after the Phase 3 APOLLO-B study met its primary and first secondary endpoint relative to placebo, as measured by the 6-Minute Walk Test (6-MWT) and the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score.

The FDA’s complete response letter indicated that the clinical meaningfulness of patisiran’s treatment effects for the cardiomyopathy of ATTR amyloidosis had not been established, and therefore, the sNDA for patisiran could not be approved in its present form. As a result of the complete response letter, Alnylam has announced it will no longer pursue an expanded indication for patisiran in the U.S.


“First and foremost, our hearts go out to patients with the cardiomyopathy of ATTR amyloidosis who are living with a rapidly progressive, debilitating and fatal disease and face significant unmet need. While we are disappointed by this decision, we are committed to supporting them and are well positioned to address their needs with continued innovation that can potentially help improve their outcomes and treatment experience,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam Pharmaceuticals

Alnylam will continue to focus on the HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic subcutaneously administered once every three months in development for the treatment of the cardiomyopathy of ATTR amyloidosis, and ALN-TTRsc04, which utilizes the Company’s IKARIA technology, with the potential for greater than 90% TTR knockdown with once annual dosing.

Patisiran is an intravenously administered treatment classified as an “RNA interference” drug. The treatment targets and silences messenger RNA, aiming to reduce the production of TTR protein before it is made.

“The data from the APOLLO-B study demonstrate the safety of ONPATTRO in patients with ATTR cardiac amyloidosis,” says Ahmad Masri, M.D., M.S., Cardiologist, OHSU Center for Hypertrophic Cardiomyopathy and Amyloidosis. “Unfortunately, the efficacy data are limited by the trial design and the short duration of follow-up, which explains the FDA’s decision. We remain excited to see the results from the other two ongoing silencers programs in development.”

The APOLLO-B trial is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the effects of ONPATTRO (patisiran) on the functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy at 69 sites in 21 countries. Patients were randomized 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every three weeks over a 12-month treatment period. After 12 months, all patients received patisiran in an open-label extension period.

“This disappointing result for those suffering from cardiomyopathy of ATTR amyloidosis highlights the need for the amyloidosis community to partner together across stakeholder groups to define how we can design meaningful trials that bring effective therapies to patients sooner,” says Isabelle Lousada, ARC Founder and CEO. “While the ATTR treatment landscape has changed dramatically over the past 5 years, ATTR cardiac amyloidosis remains a complex condition to study and one with considerable unmet need. ATTR amyloidosis will continue to have a profound impact on the physical function, activities of daily living, as well as social and emotional wellbeing of patients and requires an urgent push for more solutions.”

In 2018, ONPATTRO® (patisiran) was approved for the treatment of polyneuropathy of hereditary ATTR. If you or someone you care for currently takes ONPATTRO® (patisiran) for the treatment of polyneuropathy of hereditary ATTR, continue receiving treatment as prescribed.

Patisiran should be administered by a healthcare professional. Administration is usually done in a hospital or clinic setting, but home infusion may be an option for some patients. The decision for a patient to receive hospital/clinic or home infusions should be made after an evaluation and recommendation by the treating physician. Home infusion may not be covered by all insurance plans.

Learn more about ONPATTRO® (Patisiran) for the treatment of polyneuropathy of hereditary ATTR here.

Learn about hereditary ATTR amyloidosis here.

Learn about Wild-Type ATTR amyloidosis here.