Alnylam Pharmaceuticals, Inc., suspended a phase II trial of its investigational RNA inhibitor fitusiran for patients with hemophilia after a patient with hemophilia A experienced a fatal thrombotic event while enrolled in the open-label extension study, which was assessing fitusiran in patients with hemophilia A or B with or without inhibitors. The hold also affects the phase III ATLAS study, which was recently initiated but had not yet started dosing.
The drug’s manufacturer did not indicate whether the death was directly related to fitusiran use. Approximately nine days prior to hospital admission, the patient developed exercise-induced right hip pain that was treated with a total of three doses of factor VIII (FVIII) concentrate (31-46 IU/kg) on three separate days. Over a 14-day hospitalization, the patient’s medical condition worsened despite receiving FVIII, and the patient died from subsequent cerebral edema. The investigators reported the initial diagnosis of subarachnoid hemorrhage as unrelated to fitusiran treatment, but further analysis of computed tomography scans confirmed that the triggering event was a cerebral venous sinus thrombosis, according to Alnylam.
The company is conducting a safety review of the trial with the U.S. Food and Drug Administration to investigate a possible connection between the drug and serious thrombotic events and to develop a risk-mitigation plan.
Source: Alnylam press release, September 7, 2017.