Pfizer Inc. (NYSE: PFE) announced positive topline results from the Phase 3 AFFINE study (NCT04370054), which evaluated giroctocogene fitelparvovec, an investigational gene therapy for treating adults with moderately severe to severe hemophilia A. The AFFINE study met its primary objective, demonstrating non-inferiority and superiority in total annualized bleeding rate (ABR) from Week 12 through at least 15 months post-infusion compared to routine Factor VIII (FVIII) replacement prophylaxis treatment.
Following a single 3e13 vg/kg dose, the therapy significantly reduced mean total ABR compared to the pre-infusion period (1.24 vs 4.73; one-sided p-value=0.0040). The key secondary endpoints were also achieved, with 84% of participants maintaining FVIII activity above 5% at 15 months post-infusion (one-sided p-value = 0.0086).
The majority of participants had FVIII activity of at least 15%, and the mean treated ABR showed a significant 98.3% reduction from 4.08 pre-infusion to 0.07 post-infusion (from Week 12 up to at least 15 months; one-sided p-value < 0.0001). Only one participant (1.3%) returned to prophylaxis post-infusion. These results underscore the potential of giroctocogene fitelparvovec to transform hemophilia A treatment, providing superior bleed protection compared to routine FVIII prophylaxis while reducing treatment burden.
Safety and Tolerability
In the AFFINE study, giroctocogene fitelparvovec was generally well tolerated. Transient elevated FVIII levels ≥150% were observed in 49.3% of dosed participants, with no impact on efficacy and safety results. Serious adverse events were reported in 15 patients (20%), including 13 events in 10 patients (13.3%) deemed related to treatment. These adverse events generally resolved with clinical management, indicating a manageable safety profile for the gene therapy.
Professor Andrew Leavitt, M.D., AFFINE lead investigator and director of the Adult Hemophilia Treatment Center at the University of California, San Francisco, emphasized the significant impact of these results. He noted that the physical and emotional burden of frequent IV infusions or injections for bleeding prevention and treatment cannot be underestimated. The positive results from the AFFINE trial suggest that giroctocogene fitelparvovec could provide transformative bleed protection, offering a promising new option for people living with hemophilia A.
Giroctocogene fitelparvovec is a novel investigational gene therapy that includes a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The goal is for patients to produce FVIII themselves for an extended period, reducing the need for routine prophylaxis with intravenous infusions or injections.
Pfizer’s Commitment to Hemophilia Treatment
James Rusnak, M.D., Ph.D., Senior Vice President and Chief Development Officer of Internal Medicine and Infectious Diseases at Pfizer, expressed satisfaction with the Phase 3 results. He highlighted Pfizer’s 40-year history in advancing hemophilia treatment and the company’s commitment to reducing the medical and treatment burden associated with frequent IV infusions or injections. The successful outcomes from this trial are a significant step toward offering a one-time gene therapy for hemophilia A patients.
Eligible participants were first enrolled in a lead-in study (NCT03587116) and, upon successful completion, received a one-time 3e13 vg/kg dose of giroctocogene fitelparvovec in the AFFINE study. Participants were screened with a validated assay to identify those negative for neutralizing antibodies to the gene therapy vector. The study includes a long-term follow-up of up to 15 years to ensure comprehensive evaluation of the therapy’s efficacy and safety.
The AFFINE study’s primary endpoint measured total ABR from Week 12 through at least 15 months post-treatment compared to prior FVIII prophylaxis. Pfizer plans to present further analyses of the full Phase 3 dataset at upcoming medical meetings. Giroctocogene fitelparvovec has received Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA, as well as Orphan Drug designations in the U.S. and the EU. Pfizer will discuss the data with regulatory authorities in the coming months.
Broader Impact and Regulatory Landscape
Pfizer’s recent FDA approval of BEQVEZâ„¢ (fidanocogene elaparvovec) for hemophilia B, along with approvals in Canada and pending decisions in the EU, demonstrates the company’s continued progress in gene therapy. Additionally, regulatory submissions for marstacimab, a potential subcutaneous therapy for hemophilia A and B, are currently under review by the FDA and the EMA. Hemophilia A is an inherited bleeding disorder causing prolonged bleeding due to a deficiency in clotting factor VIII (FVIII).
It affects approximately 25 in every 100,000 male births globally, with 55-75% having moderate to severe forms. The condition increases the risk of spontaneous bleeding and bleeding following injuries or surgery, requiring constant monitoring and therapy. Pfizer’s advancements aim to alleviate these challenges by offering innovative treatments. Pfizer’s dedication to scientific innovation and improving patient lives is evident in its extensive research and development efforts. The company’s 175-year history showcases a commitment to advancing wellness, prevention, treatments, and cures for the most challenging diseases.
Pfizer collaborates with healthcare providers, governments, and communities to expand access to reliable and affordable healthcare worldwide. The positive Phase 3 results for giroctocogene fitelparvovec mark a significant milestone in hemophilia A treatment. This innovative gene therapy shows promise in providing long-term bleed protection and reducing treatment burdens, aligning with Pfizer’s mission to advance hemophilia care and improve patient outcomes.
Resource: Pfizer, July 24, 2024
This article has been prepared with the assistance of AI and reviewed by an editor. For more details, please refer to our Terms and Conditions. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author.
