Rare Disease Report

Alynlam's Hemophilia Program On Hold Following Patient Death

SEPTEMBER 07, 2017
James Radke
Alynlam’s hemophilia clinical program testing fitusiran in patients with either hemophilia A or B has been put on hold following the death of a patient in 1 of the company’s trials.

In a news conference, Akshay Vaishnaw, M.D., Ph.D., vice president of research and development noted that the deceased patient was part of a phase 2 open-label extension study in which participants were receiving monthly subcutaneous injections of fitusiran (50 or 80 mg).

Hemophilia A and hemophilia B are hereditary bleeding disorders in which patients have insufficient amounts of factor VIII and factor IX, respectively. In the United States, approximately 20,000 people have hemophilia A and 4,000 have hemophilia B. Standard treatment for these patients is factor replacement therapy. Fitusiran is an RNAi (RNA interference) drug targeting antithrombin that in turn would increase thrombin levels, restore hemostasis, and prevent bleeding in both hemophilia A and B patients.

The fatality occurred in a patient with hemophilia A who was receiving fitusiran. Initially, the patient developed exercise-induced right hip pain that was treated with a total of 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days. During the 3rd dose of factor VIII, the patient developed a severe headache. CT imaging led to a diagnosis of subarachnoid hemorrhage and the patient was hospitalized and given factor VIII concentrate 2 to 3 times daily. The patient’s condition continued to worsen and 2 weeks after being hospitalized, the patient died from cerebral edema.

Initially, the treating physician diagnosed the patient with a subarachnoid hemorrhage that was unrelated to fitusiran however, further analysis of the CT scans indicate that the patient had cerebral venous sinus thrombosis. Based on that new evidence, the company has suspended all clinical trials with fitusiran to determine if the drug is associated with adverse event or not.

"We are deeply saddened to learn of this patient’s death, and we extend our sympathies to his family," said Dr Vaishnaw. "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."

Fitusiran clinical studies include the ongoing Phase 2 open-label extension study of hemophilia A and B patients with and without inhibitors and the ATLAS Phase 3 program, the latter of which has not yet begun dosing its patients.
The Phase 3 ATLAS studies currently on hold include:

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