Alnylam has suspended dosing in trials of RNAi drug fitusiran after a patient with hemophilia A died in one of the studies. The biotech is now developing a strategy to mitigate the risk of more patients suffering fatal blood clots before resuming the trials.
Cambridge, Massachusetts-based Alnylam is hoping to get the studies back up and running soon, potentially before the end of the year. First, the gene-silencing specialist needs to come up with changes to its study protocols that enhance patient safety monitoring and allay any worries regulators may have about the safety of fitusiran.
The safety red flag—and possible doubts it raises about Alnylam’s pipeline—has popped up at an inopportune moment for Alnylam, which has the eyes of the biotech world upon it as it closes in on the publication of phase 3 data on patisiran. Over the past year, Alnylam has halted work on one RNAi drug—revusiran—and seen the prospects of another dented by deaths and side effects.
The worst-case scenario is the latest patient death has implications for Alnylam’s other RNAi drugs. But there is a rationale for the thrombotic event being tied to the knocking down of antithrombin, not gene-silencing in general.
Either way, Alnylam now faces a race to get fitusiran back on track. The death occurred in a phase 2 open-label extension study. But Alnylam was also ready to start enrolling patients in its phase 3 Atlas program. That late-phase trial is now on hold. In the longer term, the safety issue means Alnylam may face an uphill struggle to win over hemophilia patients. These patients are typically defined as risk averse and have access to a growing pool of treatment options.
Alnylam thinks the overall risk-benefit profile of fitusiran suggests it can muscle in on the market nonetheless and is working to clear the recently erected barriers between it and the data it needs.
The biotech put up those barriers after a series of events, thought to be triggered by cerebral venous sinus thrombosis, put a patient with hemophilia A in the hospital and ultimately resulted in his death.
"We are deeply saddened to learn of this patient’s death, and we extend our sympathies to his family," Alnylam EVP Akshay Vaishnaw, M.D., Ph.D., said 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.”
Shares in Alnylam fell 10% in premarket trading.