FDA Expands Patisiran’s Orphan Drug Status to Another Form of Familial Amyloidosis

The U.S. Food and Drug Administration has agreed to Alnylam Pharmaceuticals’ request to expand the orphan drug designation for patisiran to include a second type of familial amyloidosis.

Patisiran’s original orphan designation was for familial amyloidotic polyneuropathy, the most common form of the disease. The new designation covers a form known as transthyretin-mediated amyloidosis, or ATTR amyloidosis. The FDA grants orphan status to therapies for rare diseases.

“The expansion of the orphan drug designation demonstrates the recognition of ATTR amyloidosis as a broad-spectrum disease impacting multiple body organs and tissue,” Eric Green, the vice president and general manager of Alnylum’s TTR program, said in a press release. Mutations of the TTR gene produce a faulty version of the transthyretin protein associated with ATTR amyloidosis.

Alnylam also plans to file a New Drug Application for patisiran as a treatment for familial ATTR amyloidosis. The application is an official request that the FDA begin the regulatory process for the drug.

“We look forward to completing the NDA [New Drug Application] submission by year-end and working with the FDA to potentially bring the first FDA-approved RNAi therapeutic to patients living with hereditary ATTR amyloidosis,” Green said. An RNAi therapy prevents a gene from producing a faulty version of a protein.

Alnylam worked with Sanofi Genzyme to develop patisiran.

Accumulations of abnormal transthyretin protein damage the nerves, heart and gastrointestinal tract and generate the symptoms that characterize the disease.

Patisiran binds to the messenger RNA molecule that codes for the protein, preventing the TTR gene from producing the faulty version.

In November of this year, the FDA gave patisiran Breakthrough Therapy designation as a treatment for hereditary ATTR amyloidosis with polyneuropathy. The designation expedites the development and regulatory process for therapies that deal with serious or life-threatening conditions.

The European Medicines Agency also gave patisiran accelerated assessment status this year.

Alnylam and Sanofi Genzyme plan to file a marketing application for the drug with the European Union before the end of 2017.

Under the companies’ partnership, Alnylam is responsible for commercializing patisiran in the United States, Canada and Western Europe. Sanofi Genzyme is in charge of commercialization in the rest of the world, including Central and Eastern Europe.

Sanofi plans to ask Japan, Brazil and other countries’ regulators to approve partisan in the first half of 2018.

The FDA and European Union based their recent decisions on patisiran on the results of the APOLLO Phase 3 clinical trial (NCT01960348) and the long-term extension of a Phase 2 trial (NCT01961921). They showed that patisiran reduced the impairment the disease generates and improved patients’ quality of life.