Regulatory Affairs

Alnylam, Sanofi submit MAA to EMA for patisiran to treat hereditary ATTR amyloidosis

Published 19 December 2017

Alnylam Pharmaceuticals and Sanofi Genzyme have submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for patisiran, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of adults with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis).

Patisiran was previously granted accelerated assessment by the EMA, potentially reducing the Agency’s evaluation time from 210 to 150 days.

“The MAA submission for patisiran represents another important milestone for Alnylam and a critical step toward bringing RNAi therapeutics to people living with hATTR amyloidosis,” said Eric Green, Vice President and General Manager of the TTR program at Alnylam.

“Based on the results of the APOLLO study, we believe patisiran has the potential to become the standard of care for the treatment of hATTR amyloidosis. We look forward to working with the EMA and the Committee for Medicinal Products for Human Use (CHMP) during the review process.”

“People with hATTR amyloidosis have limited treatment options,” said Rand Sutherland, M.D., Therapeutic Area Head, Rare Diseases Development at Sanofi. “With this MAA submission, we are one step closer to making patisiran available in Europe and executing on our shared vision to bring this RNAi treatment to patients globally.”

Alnylam announced completion of the submission of a New Drug Application with the U.S. Food and Drug Administration on December 12, 2017. Sanofi Genzyme is currently preparing regulatory filings for patisiran in Japan, Brazil and other countries, with submissions expected to begin in the first half of 2018.

Pending regulatory approvals, Alnylam will commercialize patisiran in the U.S., Canada and Western Europe, with Sanofi Genzyme commercializing the product in the rest of the world, including certain Central and Eastern European countries of the European Union.

Patisiran is an investigational intravenously administered RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of hereditary ATTR amyloidosis. It is designed to target and silence specific messenger RNA, potentially blocking the production of TTR protein before it is made.

This may help to enable the clearance of TTR amyloid deposits in peripheral tissues and potentially restore function to these tissues. The safety and efficacy of patisiran have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

The APOLLO Phase 3 study (N=225) was a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in hATTR amyloidosis patients with polyneuropathy. The study was completed in August 2017 and detailed study results were presented at the 1st European ATTR Amyloidosis Meeting for Patients and Doctors on November 2, 2017. All patients completing the APOLLO Phase 3 study are eligible to screen for the Global OLE study, in which they have the opportunity to receive patisiran on an ongoing basis.

Hereditary transthyretin (TTR)-mediated (hATTR) amyloidosis is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier of vitamin A.

Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. hATTR amyloidosis represents a major unmet medical need with significant morbidity and mortality, affecting approximately 50,000 people worldwide.

hATTR amyloidosis patients have a life expectancy of 2.5 to 15 years from symptom onset, and the only approved treatment options are liver transplantation for early stage disease and tafamidis (approved in Europe, Japan and certain countries in Latin America, specific indication varies by region). There is a significant need for novel therapeutics to help treat patients with hATTR amyloidosis.

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

In January 2014, Alnylam and Sanofi Genzyme, the specialty care global business unit of Sanofi, formed an alliance to accelerate the advancement of RNAi therapeutics as a potential new class of innovative medicines for patients around the world with rare genetic diseases.

The alliance enables Sanofi Genzyme to expand its rare disease pipeline with Alnylam’s novel RNAi technology and provides access to Alnylam’s R&D engine, while Alnylam benefits from Sanofi Genzyme’s proven global capabilities to advance late-stage development and, upon commercialization, accelerate market access for these promising genetic medicine products.



Source: Company Press Release