Officials of the U.S. Food and Drug Administration and Alnylam Pharmaceuticals have agreed on safety measures and a “risk mitigation strategy” to allow the resumption of clinical studies of fitusiran, the company said in a recent press release.
All ongoing trials of fitusiran had been suspended after the Sept. 7 death of a patient with hemophilia A who was receiving fitusiran in the Phase 2 Open-Label Extension study (NCT02035605). Neither the FDA nor the European Medicines Agency nor any other regulatory authority have approved Fitusiran, and no conclusions can be drawn yet regarding its safety or effectiveness.
Alnylam, based in Cambridge, Massachusetts, aims to proceed with testing of fitusiran, including the Phase 2 open-label extension (OLE) study and the ATLAS Phase 3 program, once it gets the go-ahead from the FDA. The ATLAS program comprises three different trials of fitusiran in patients with hemophilia A and B, with or without inhibitors, including those on prophylactic (preventive) therapy. Hemophilia patients sometimes develop antibodies, called inhibitors, that inhibit the blood-clotting factors provided in standard replacement therapy.
Fitusiran (ALN-AT3SC) is a new approach to treating hemophilia by targeting a protein called antithrombin (AT) that stops blood clotting. Fitusiran is designed to lower the levels of antithrombin in hemophilia patients to let blood clotting occur and thereby prevent bleeding.
Fitusiran is an investigational RNA interference (RNAi) therapeutic, a new class of drugs that act by targeting specific substances called messenger ribonucleic acids (mRNAs). These act at one stage of the process of producing proteins. Fitusiran stops mRNAs that help produce AT.
“We are pleased with the outcome of our meeting with the FDA regarding next steps for the fitusiran clinical program and remain committed to reinitiating the Phase 2 OLE and the Phase 3 ATLAS program around year-end,” said Dr. Akin Akinc, vice president and general manager for Alnylam’s fitusiran division. “Further, we look forward to continuing our partnership with physicians and nurses to support education efforts on fitusiran safety, which we believe are a critical step when introducing a new therapeutic modality with the potential to address important unmet needs in hemophilia.”
In January 2014, Alnylam and Sanofi Genzyme formed an alliance to speed up the advancement of RNAi therapeutics as a new class of medicines for patients with rare genetic diseases.