Pfizer’s Hemophilia A Trial Shows Superiority Over FVIII Prophylaxis

Pfizer’s phase 3 AFFINE study (NCT04370054) evaluating giroctocogene fitelparvovec, an investigational gene therapy for the treatment of adults with moderately severe to severe hemophilia A, has met its primary endpoint of demonstrating non-inferiority, as well as superiority, of total annualized bleeding rate (ABR) from Week 12 through at least 15 months of follow up post-infusion compared with routine Factor VIII (FVIII) replacement prophylaxis treatment.¹

“For people living with hemophilia A, the physical and emotional impact of needing to prevent and treat bleeding episodes through frequent IV infusions or injections cannot be underestimated,” lead investigator Andrew Leavitt MD, Professor, Departments of Laboratory Medicine and director, Medicine Division of Hematology/Oncology, Adult Hemophilia Treatment Center, University of California, San Francisco, California, said in a statement.¹ “I’m excited by the strength of these positive results from the AFFINE trial that show giroctocogene fitelparvovec was generally well tolerated, and demonstrate the transformative potential of this gene therapy candidate to provide superior bleed protection compared with routine FVIII prophylaxis, while helping relieve the treatment burden for people living with hemophilia A.”

Participants experienced a statistically significant reduction in mean total ABR compared to the pre-infusion period (1.24 vs 4.73; one-sided P = .0040) after receiving a single 3e13 vg/kg dose of giroctocogene fitelparvovec. The AFFINE study also met key secondary endpoints, including 84% of participants maintaining FVIII activity >5% at 15 months post-infusion (one-sided P = .0086) with the majority of participants having FVIII activity ≥15%, and a statistically significant 98.3% reduction from 4.08 in the pre-infusion period to 0.07 post-infusion (from Week 12 up to at least 15 months [range, 15-44]; one-sided P <.0001) in the mean treated ABR. Only 1 of all dosed participants (1.3%) returned to prophylaxis post-infusion. The full data readout from AFFINE will be presented at upcoming medical meetings.

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“We are very pleased with these positive results from the Phase 3 AFFINE study demonstrating the safety and efficacy of our one-time gene therapy candidate for people with hemophilia A,” James Rusnak, MD, PhD, Senior Vice President, Chief Development Officer, Internal Medicine and Infectious Diseases, Research and Development, Pfizer, added.¹ “We look forward to advancing this latest innovation to help address the medical and treatment burden associated with frequent and time-consuming IV infusions or injections, building on Pfizer’s more than 40-year effort to advance hemophilia treatment.”

Study participants had a manageable safety profile with giroctocogene fitelparvovec treatment. Around half (49.3%) of participants had transient elevated FVIII levels ≥150% as measured via chromogenic assay; these levels did not impact efficacy and safety results. Serious adverse events(AEs) occurred in 15 patients (20%) and 13 AEs reported by 10 participants (13.3%) were deemed related to treatment. These AEs generally resolved with clinical management.¹

“We are thrilled with the positive topline results from the Phase 3 AFFINE trial, which demonstrated the potential of giroctocogene fitelparvovec as a one-time gene therapy for people with hemophilia A and provide a potential alternative to the current burden of disease management,” Nathalie Dubois-Stringfellow, PhD, Chief Development Officer, Sangamo Therapeutics, said in a statement.² Giroctocogene fitelparvovec is codeveloped by Sangamo and licensed to Pfizer.

“These impressive results further validate the power of our genomic technologies and take us one step closer towards what could become Sangamo’s first medicine commercially available to patients. We greatly appreciate Pfizer’s strong leadership of this important program and look forward to their discussions of these data with regulatory authorities,” Dubois-Stringfellow added.²

Pfizer’s fidanacogene elaparvovec-dzkt gene therapy was approved under the name Beqvez in April 2024 for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid determined by an FDA-approved test. The therapy comes with a price tag of $3.5 million.³

REFERENCES

1. Pfizer Announces Positive Topline Results From Phase 3 Study of Hemophilia A Gene Therapy Candidate. News release. July 24, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-results-phase-3-study
2. Sangamo Therapeutics Reports on Pfizer’s Announcement of Positive Topline Results From Phase 3 Trial of Hemophilia A Gene Therapy Candidate. News release. Sangamo Therapeutics. July 24, 2024. https://www.businesswire.com/news/home/20240724053258/en/Sangamo-Therapeutics-Reports-on-Pfizer%E2%80%99s-Announcement-of-Positive-Topline-Results-From-Phase-3-Trial-of-Hemophilia-A-Gene-Therapy-Candidate
3. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogeneelaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. News release. Pfizer. April 26, 2024. Accessed April 26, 2024. https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B