- Pfizer and Sangamo said they have started a Phase 3 trial of their gene therapy to treat hemophilia A, announcing Wednesday that more than 60 patients will receive a single dose to detect whether it can reduce bleeding episodes compared to previous treatment using clotting factors.
- The trial will measure the annual bleed rate for the first 12 months after receiving a dose of the gene therapy as its primary outcome. A rival project from BioMarin Pharmaceutical was rejected by the Food and Drug Administration in August after regulators asked for two-year follow-up to evaluate the whether the treatment's benefits hold up.
- The FDA's decision on BioMarin's candidate signaled that the agency could be tougher on gene therapies for hemophilia than it was on the first two that gained approval, which were for disorders with no alternative treatments. Hemophilia patients today can reduce the number of bleeding episodes they experience by taking drugs that replace missing blood-clotting proteins, although they are very expensive.
Hemophilia has been an early target of gene therapy developers because of its rarity, its burden, and the fact that it is caused by a single mutation. These characteristics were also true of the first two diseases with gene therapies approved by the FDA, Luxturna and Zolgensma, but the difference in the agency's review of BioMarin's hemophilia project Roctavian is that regulators could compare it to factor replacement therapies like Takeda's Advate, along with newer drugs like Roche's Hemlibra.
The promise of gene therapy is a once-and-done treatment that will reduce or even eliminate disease. Developers hope that this promise will justify a high price, since they will be replacing frequently administered drugs that can cost more than gene therapy over patients' lifetimes
But because these treatments haven't been used in humans very long, there is still skepticism over whether they will be durable. That's the question BioMarin ran headlong into during its FDA review.
Now Pfizer and Sangamo will take their shot. Their Phase 3 trial will measure the annualized bleeding rate 12 months following an infusion of giroctocogene fitelparvovec, a therapy previously known as SB-525. That rate will be compared to enrollees' bleeding rates in the six months before the infusion while they were getting factor replacement drugs, which they will stop taking after receiving the gene therapy.
If the FDA were to accept data at the 12-month time point, it would put giroctocogene fitelparvovec on course to launch on a similar time frame to BioMarin's, instead of trailing by two years, as would have been the case had Roctavian gained approval last month.
However, the Roctavian decision does potentially set a precedent for review of future hemophilia gene therapies. The giroctocogene fitelparvovec clinical trial will follow patients for up to five years, tracking bleeding episodes to give investigators an opportunity to measure the rate at two years, as with Roctavian.