Sangamo Reports Pfizer's Positive Phase 3 Hemophilia A Gene Therapy Results

RICHMOND, Calif.--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomics-focused medical company, has announced that Pfizer Inc. shared promising topline results from the Phase 3 AFFINE trial (NCT04370054). This trial evaluated giroctocogene fitelparvovec, an experimental gene therapy co-developed by Sangamo and Pfizer, for treating adults with moderate to severe hemophilia A.

Sangamo is set to receive up to $220 million from Pfizer if certain regulatory and commercial milestones are reached for giroctocogene fitelparvovec. Additionally, upon approval and commercialization, Sangamo could earn product sales royalties ranging from 14% to 20%, subject to specific reductions.

The AFFINE trial's primary objective was to demonstrate the non-inferiority and superiority of giroctocogene fitelparvovec in reducing the annualized bleeding rate (ABR) from Week 12 through at least 15 months post-infusion, compared to routine Factor VIII (FVIII) replacement prophylaxis. The results showed a statistically significant reduction in mean total ABR, dropping from 4.73 in the pre-infusion period to 1.24 post-infusion (one-sided p-value=0.0040).

Secondary endpoints also confirmed the superiority of the gene therapy over prophylaxis. An impressive 84% of participants maintained FVIII activity above 5% at 15 months post-infusion (one-sided p-value = 0.0086), with many showing FVIII activity levels of 15% or higher. Furthermore, the mean treated ABR showcased a dramatic 98.3% reduction from 4.08 before the infusion to 0.07 afterwards (one-sided p-value < 0.0001). Only one participant (1.3%) resumed prophylactic treatment post-infusion during the entire trial period.

Safety and tolerance of giroctocogene fitelparvovec were also assessed in the trial. Elevated FVIII levels of ≥150% were seen in 49.3% of participants, yet this did not affect the therapy's efficacy or safety. Serious adverse events were reported in 20% of participants, with 13 events in 10 patients directly linked to the treatment. Most treatment-related adverse effects resolved with clinical management.

Prof. Andrew Leavitt, M.D., the lead investigator for AFFINE, emphasized the significant impact of these results for those living with hemophilia A. The gene therapy demonstrated potential as a superior alternative to routine FVIII prophylaxis, offering better protection against bleeding episodes and reducing the treatment burden.

Giroctocogene fitelparvovec comprises a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The aim is for patients to produce their own FVIII after a single infusion, potentially eliminating the need for regular prophylactic IV infusions or injections.

Dr. Nathalie Dubois-Stringfellow, Chief Development Officer at Sangamo, expressed enthusiasm about the positive results, which mark a significant milestone towards Sangamo’s first commercially available medicine. She acknowledged Pfizer's crucial role in the development and anticipated regulatory discussions based on these data.

Participants in the AFFINE trial initially enrolled in a lead-in study (NCT03587116) and, upon completion, received a one-time 3e13 vg/kg dose of giroctocogene fitelparvovec. They were screened for neutralizing antibodies to ensure eligibility, and will be monitored for a total of up to 15 years as part of a long-term follow-up.

Pfizer is continuing to analyze the full dataset from this Phase 3 trial and will present additional data at future medical conferences. Giroctocogene fitelparvovec has received Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. FDA, along with Orphan Drug status in both the U.S. and the EU. Pfizer intends to engage with regulatory authorities in the coming months.

The AFFINE trial (NCT04370054) is an open-label, multicenter, single-arm study assessing giroctocogene fitelparvovec’s efficacy and safety in adult males with moderately severe to severe hemophilia A. The primary endpoint focuses on the total ABR from Week 12 through at least 15 months post-treatment, compared to prior FVIII prophylaxis.

Giroctocogene fitelparvovec’s development results from a collaboration between Sangamo Therapeutics and Pfizer. In 2019, Sangamo transferred manufacturing technology and the Investigational New Drug application to Pfizer, which now handles pivotal studies, regulatory activities, and potential global commercialization.