Alnylam Pharmaceuticals, Inc. has reported on the death of a hemophilia A patient who had been participating in a Phase 2 open label extension study for the company’s investigational therapy fitusiran which is being developed for patients with hemophilia A and B, both with or without inhibitors.

Fitusiran is a subcutaneous therapy (administered under the skin) that employs small interfering RNA (siRNA) technology to target antithrombin (AT), a liver-generated clotting protein that plays a key role in the regulation of blood clots. siRNA molecules are segments of RNA (ribonucleic acid) that block or “silence” the activity of certain genes through RNA interference, a natural biological process common in plants and mammals. Fitusiran works by silencing the gene responsible for AT, which inhibits the protein’s anticoagulant function. This then compensates for the imbalance caused by deficiencies in other clotting proteins, such as factor VIII (hemophilia A) or factor IX (hemophilia B).

According to the September 7, 2017 press release, Alnylam has halted dosing in all ongoing fitusiran studies in order to conduct a thorough review of the case. In the meantime, the company has provided some background. While initial findings suggested that the patient had died from subarachnoid hemorrhage, further analysis of CT scans confirmed that the triggering event was actually a cerebral venous sinus thrombosis (CVST). A CVST is a blood clot that develops in the venous sinuses of the brain, which prevents blood from draining out. This blood subsequently leaks into the brain tissues, resulting in a hemorrhage. Such an event, albeit rare, is very serious and can result in a stroke.

“We are deeply saddened to learn of this patient’s death, and we extend our sympathies to his family,” said Akshay Vaishnaw, MD, PhD, Executive Vice President of R&D at Alnylam. “We believe that fitusiran holds great promise as a potential treatment option for patients with hemophilia, and we remain fully committed to its ongoing development. Following further investigation of this safety finding, implementation of a risk mitigation strategy, and alignment with global regulatory authorities, we expect to resume fitusiran dosing in our clinical studies as soon as possible, potentially as early as late 2017, with a goal of advancing this innovative investigational medicine to hemophilia patients in need.”

It is not yet known if this event is directly related to the patient’s treatment with fitusiran. The National Hemophilia Foundation will continue to monitor this case and will provide updates as they become available.

Source: Alnylam press release dated September 7, 2017