Pfizer’s research partnership with Sangamo Therapeutics produced a hemophilia A gene therapy that reached FDA discussions about a regulatory submission. That’s as far as the alliance will go. Pfizer is terminating the seven-year-old pact, a move that comes before the pharmaceutical giant must pay costly milestone payments for a product with uncertain commercial prospects.
According to Sangamo, Pfizer said the termination reflects its decision to not go forward with regulatory submissions for the hemophilia A gene therapy, giroctocogene fitelparvovec. The termination was announced after Monday’s market close. When the termination takes effect in April, Sangamo will regain all rights to the gene therapy. The Richmond, California-based biotech said it still aims to advance the program and will explore all options, including seeking a new collaboration partner to take the therapy through regulatory review and commercialization.
Giroctocogene fitelparvovec is a functioning version of the gene that codes for factor VIII, the clotting protein that’s deficient in hemophilia A patients. The one-time treatment is intended to enable patients to produce factor VIII, bringing that protein closer to normal levels. Under the collaboration agreement signed in 2017, Sangamo was responsible for Phase 1/2 development of the gene therapy. Pfizer’s responsibility spanned late-stage development, regulatory submissions, and commercialization.
This past summer, Pfizer reported preliminary Phase 3 results showing the gene therapy led to statistically significant reductions in annualized bleeding rates through 15 months. The pharma giant said it planned to meet with regulators. According to Sangamo, Pfizer had said it expected U.S. and European regulatory submissions would happen in early 2025. As recently as last month, Pfizer indicated it was discussing the data with regulators.
Hemophilia gene therapies have made it through regulatory review. Pfizer did it earlier this year, winning FDA approval for Beqvez, a hemophilia B gene therapy that was licensed from Spark Therapeutics. But commercializing pricey hemophilia gene therapies has proven to be difficult. For patients who can manage hemophilia with infusions of clotting proteins or chronic dosing of certain drugs, one-time treatment from gene therapy has been a tough sell. Newer hemophilia drugs are entering the market, giving patients even more choices. Pfizer has one of them with Hympavzi, a once-weekly injectable drug approved by the FDA in October for both hemophilia A and B.
The commercialization challenges facing hemophilia gene therapies are forcing companies to make hard choices. Lackluster sales of Roctavian, a BioMarin Pharmaceutical gene therapy for hemophilia A approved last year, have led that company to explore options including divestiture of the product. Now Pfizer has decided not to proceed with Sangamo’s hemophilia A gene therapy.
Under the gene therapy alliance, Sangamo received $70 million up front. According to the biotech’s financial reports, it had received $55 million in milestone payments so far. Up to $220 million in additional milestone payments remained outstanding. Sangamo was counting on the Pfizer payments for its survival.
Collaborations with Novartis and Biogen ended last year, leading Sangamo to implement a corporate restructuring and layoffs. Sangamo has since inked deals with Genentech and Astellas Pharma, but these agreements come with small upfront payments and milestones that may be years away. In its financial reports, Sangamo said it has explored the possibility of filing for bankruptcy protection. The company’s cash position as of Sept. 30 was $39.2 million, according to its report for the third quarter of 2024. Sangamo said it expected to have enough cash to last only into the first quarter of 2025.
Sangamo needs cash to support its pipeline of neurology genomic medicines, including a gene therapy for Fabry disease. In October, the FDA confirmed to the company that Phase 1/2 data would be sufficient to support a regulatory submission under the accelerated approval pathway. The company planned a submission for the second half of 2025.
In the announcement of the Pfizer termination, Sangamo said it believes it can chart a path forward for its programs, but the company acknowledged that additional funding is necessary for advancing each of them, including the hemophilia A gene therapy. In a prepared statement, Sangamo CEO Sandy Macrae said the company was surprised and disappointed by Pfizer’s decision to end the collaboration so close to the expected regulatory submissions.
“We are committed to exploring the optimal path forward for this important treatment, including seeking the right partner with the focus and understanding of the genomic medicine commercial environment to bring this medicine to patients,” he said.
Illustration: Kuzma, Getty Images
