FDA Lifts Clinical Hold on Investigational Therapy Fitusiran

The U.S. Food and Drug Administration (FDA) has lifted the hold on clinical studies with fitusiran, an investigational therapy for hemophilia, Alnylam Pharmaceuticals announced.

“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” Akin Akinc, PhD, vice president and general manager, Fitusiran at Alnylam said in a press release.

The FDA has approved amendments to the trial’s protocol, including protocol-specified guidelines and new clinical risk mitigation measures. The new guidelines focus on patient and investigator education regarding dosing for the treatment of eventual bleeds during studies of the drug.

In 2014, Alnylam Pharmaceuticals and Sanofi Genzyme established a collaboration to foster the development of RNAi therapeutics for rare genetic diseases.

Fitusiran, also known as ALN-AT3SC, is an RNAi therapeutic agent that targets and decreases the levels of antithrombin — a protein that inhibits blood clotting — while it increases the production of thrombin, a protein that aids the clotting process. Overall, fitusiran modulates the balance of clotting components to prevent bleeding episodes in hemophilia A and B patients.

RNAi-based therapeutics act by targeting specific substances called messenger ribonucleic acids (mRNAs). Fitusiran targets the mRNA of antithrombin so that the production of the protein is inhibited.

In September, Alnylam suspended patient dosing in all ongoing trials with fitusiran after a patient with hemophilia A died of swelling in the brain in the Phase 2 OLE open-label extension trial (NCT02554773).

FDA’s decision to lift the hold on fitusiran means that Alnylam can continue with its clinical program for fitusiran, specifically the OLE study and the ATLAS Phase 3 program.

The OLE study enrolled 33 patients, 27 with hemophilia A and six with hemophilia B – who received fitusiran at 50 mg or 80 mg by subcutaneous injections (under the skin). The study’s primary goal is to assess fitusiran’s long-term safety and tolerability by measuring the patients experiencing adverse events.

The ATLAS Phase 3 program includes three separate trials of fitusiran and expects to recruit patients with hemophilia A and B, with or without inhibitors, and those on prophylactic (preventive) therapy. Hemophilia patients sometime develop antibodies, also called inhibitors, that may decrease the effectiveness of standard replacement therapy.

“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end,” said Akinc.