In Week of Hemophilia News, Alnylam Drug Cleared to Move Forward

Xconomy Boston — 

The FDA has cleared Alnylam Pharmaceuticals to resume testing of an experimental hemophilia drug after instituting a variety of measures meant to manage the possible risks of taking the therapy, known as fitusiran.

Cambridge, MA-based Alnylam (NASDAQ: ALNY) can restart the Phase 3 study and Phase 2 open-label extension trials of fitusiran, a drug being developed for hemophilia A and B, as a result of the deal. The new risk-mitigating measures include “protocol-specific guidelines and additional investigator and patient education” about reducing doses of other hemophilia drugs if patients suffer any bleeds while on fitusiran. Alnylam didn’t provide more specifics.

Shares of Alnylam climbed about 5 percent in pre-market trading on Friday.

Clinical testing of the Alnylam drug was suspended in September after a patient in a clinical trial died. The death was deemed possibly related to fitusiran, but Alnylam said it was the result of a misdiagnosis—the patient was initially deemed to have a brain hemorrhage not related to the company’s drug and administered higher doses of blood clotting Factor VIII. An independent analysis performed afterwards found that the patient actually had cerebral venous sinus thrombosis, a blood clot that bursts in the brain.

Reflecting on the incident at a conference in September, CEO John Maraganore said “to some extent, we have to reeducate the hemophilia population with drugs like fitusiran” about how to handle bleeds that occur on while on Alnylam’s drug. That’s because fitusiran is already helping to clot blood—adding too much pro-clotting treatment on top of it can be dangerous. A similar issue cropped up in the clinical testing of Roche’s new hemophilia drug, emicizumab (Hemlibra), which was given a black box warning in its label from the FDA when it was approved in November.

Fitusiran is part of a new wave of therapies being developed for the chronic blood disease, which affects an estimated 40,000 people in the U.S., according to the Hemophilia Federation of America. The condition is typically treated prophylactically with infusible drugs given multiple times a week that boost levels of the clotting proteins these patients lack. But longer-lasting therapies are emerging as well. Several were showcased this past week at the American Society of Hematology’s annual meeting in Atlanta.

Alnylam’s drug, taken monthly through a subcutaneous injection, is one of those monthly drugs. Roche’s emicizumab, approved for some hemophilia A patients but potentially all of them soon, recently showed in clinical testing it may work when given once a month as well. Then there’s gene therapy, which offers the potential of a one-time, long-lasting treatment. The most advanced gene therapy, a hemophilia A drug from BioMarin Pharmaceutical (NASDAQ: BMRN), should begin late-stage testing before the end of the year. Several questions remain, but gene therapies have shown, in some cases, stunning results in patients with either hemophilia A or B.

While Alnylam’s drug will enter an increasingly competitive market, it offers some potential advantages—it is cheaper to produce than biologic drugs and can be stored at room temperature. Still, Leerink Partners analyst Paul Matteis observed in a research note that “additional safety data and the demonstration that blood clot risk is manageable will be important variables” to help gauge its commercial potential.

The drug has the chance to be the second Alnylam therapy to reach the market. Patisiran, for the rare transhtyretin amyloidosis, could become the first-ever approved RNA interference drug if the FDA approves the treatment next year.

Here’s more the emerging hemophilia therapies, and the questions they face.