September 7, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Mass. – Alnylam Pharmaceuticals updated two of its clinical programs. Perhaps most importantly, it indicated that it had suspended its Phase II trial of fitusiran for hemophilia A after a patient died from a thrombotic event, pending further investigation.
There are several ongoing clinical trials for fitusiran. One is the ongoing Phase II OLE study of hemophilia A and B with and without inhibitors, and the ATLAS Phase III trial, which has been started, but hasn’t begun patient dosing. In the OLE study, a patient with hemophilia A died from a fatal serious adverse event (SAE). About nine days before hospital admission, the patient developed exercise-induced right hip pain that was treated with three doses of factor VIII concentrate on three separate days. Four days before being admitted, when receiving the third dose, he developed a severe headache.
The patient was suspected of having viral meningitis. However, the patient was diagnosed with subarachnoid hemorrhage using CT imaging. He was treated with factor VIII concentrate two to three times per day. During the 14 days in the hospital, his condition grew worse, despite the administration of factor. The patient subsequently died from cerebral edema. Initially the diagnosis of subarachnoid hemorrhage was reported by the investigator as not related to fitusuran.
Alnylam launched an investigation that included reviewing the CT scans by three independent neuro-radiologist. All three confirmed on September 1, 2017 that the initiating event was a cerebral venous sinus thrombosis, not a subarachnoid hemorrhage. Because of these opinions, Alnylam suspended dosing in the fitusiran studies to further investigate the possibility of a connection to the drug and to develop a plan to mitigate risk.
“We are deeply saddened to learn of this patient’s death, and we extend our sympathies to his family,” said Akshay Vaishnaw, Alnylam’s executive vice president of R&D, in a statement. “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.”
In terms of its givorsiran program, an interim Phase I study showed over 80 percent reduction of urinary ALA and over 70 percent mean decrease compared to placebo in annualized number of porphyria attacks in patients with acute intermittent porphyria (AIP). Excepting porphyria attacks, three patients reported four serious adverse events, including a previously reported fatal episode of hemorrhagic pancreatitis. However, investigations determined they were not related to the drug.
The European Medicines Agency (EMA) gave the drug PRIME designations and the U.S. Food and Drug Administration (FDA) gave it Breakthrough Therapy Designation. In cooperation with the FDA, Alnylam has settled on a Phase III study design and expects to initiate the study in late 2017 with interim data available in mid-2018.
Investors, however, weren’t happy about the patient death in the fitusiran study. Shares dropped 13 percent in premarket trade this morning. Shares are currently at $86.02, although the premarket figure is $76.
