Pfizer Hemophilia A Candidate Shows Positive Topline Results

The phase 3 AFFINE study (NCT04370054) evaluating giroctocogene fitelparvovec in adults with moderately severe to severe hemophilia A achieved its primary objectives, according to a news release today from Pfizer.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,” said Andrew Leavitt, MD, lead investigator of the AFFINE study and a professor in the departments of laboratory medicine and medicine division of hematology/oncology director, adult hemophilia treatment center, at the University of California, San Francisco.

He continued, “I’m excited by the strength of these positive results…[that] 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.”

Eligible participants (n=75; 100% men) were initially enrolled in a lead-in study (NCT03587116); after successful completion, they were enrolled into the open-label, multicenter, single-arm AFFINE study.

READ MORE: Efanesoctocog alfa Prophylaxis Offers “Efficacious Prevention” to Children With Severe Hemophilia A

Investigators found that giroctocogene fitelparvovec was both noninferior and superior to routine Factor VIII (FVIII) replacement therapy in total annualized bleeding rate from week 12 through at least 15 months follow-up post infusion. A single 3e13 vg/kg dose of giroctocogene fitelparvovec “demonstrated a statistically significant reduction in mean total [annualized bleeding rate]” compared to the pre-infusion period (1.24 vs 4.73).

Giroctocogene fitelparvovec also met key secondary endpoints. Study participants maintained FVIII activity greater than 5% at 15 months post-infusion; many participants showed FVIII activity greater than or equal to 15%, while mean treated annualized bleeding rate showed a statistically significant 98.3% reduction (4.08 pre infusion vs 0.07 post infusion [week 12 to at least 15 months]).

Treatment was generally well-tolerated. Investigators evaluated transient elevated FVIII levels greater than or equal to 150% in 49.3% of dosed participants, “with no impact on efficacy and safety results.” Fifteen patients (20%) reported serious adverse events, 13 of which (in 10 patients) were related to treatment. These treatment-related adverse events “generally resolved in response to clinical management.”

“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,” said James Rusnak, MD, PhD, senior vice president and chief development officer, internal medicine and infectious diseases, research and development, Pfizer. “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.”

READ MORE: Slideshow: 2023 Biologic Product Approvals

Ggiroctocogene fitelparvovec is a novel investigational therapy containing a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The goal of this treatment is that just a single dose of giroctocogene fitelparvovec allows patients with hemophilia A to produce FVIII for an extended period.

Analyses of the full phase 3 dataset are ongoing, with additional data to be presented at upcoming medical meetings. The FDA has granted giroctocogene fitelparvovec Fast Track, Orphan Drug, and Regenerative Advanced Medicine designations.

These positive results for a hemophilia A therapy follow the recent approval of fidanocogene elaparvovec (Beqvez), the company’s hemophilia B therapy on April 26, 2024.² The FDA is also reviewing regulatory submissions for marstacimab, a novel subcutaneous therapy for the treatment of individuals with hemophilia A and B with and without inhibitors.³

READ MORE: Rare Disease Resource Center

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References

1. Pfizer announces positive topline results from phase 3 study of hemophilia A gene therapy candidate. News release. Pfizer. July 24, 2024. Accessed July 24, 2024. https://www.businesswire.com/news/home/20240724525239/en/Pfizer-Announces-Positive-Topline-Results-From-Phase-3-Study-of-Hemophilia-A-Gene-Therapy-Candidate

2. US FDA approves Pfizer’s Beqvez (fidanacogene elaparvovec-dzkt), a one-time gene therapy for adults with hemophilia B. News release. Pfizer. April 26, 2024. Accessed July 24, 2024. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec

3. Pfizer announces positive marstacimab results from pivotal phase 3 hemophilia A and B trial. News release. Pfizer. May 30, 2023. July 24, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-marstacimab-results-pivotal-phase