Pfizer Announces Positive Topline Results From Phase 3 Study of Hemophilia A Gene Therapy Candidate
Giroctocogene fitelparvovec study meets primary and key secondary objectives of superiority compared to prophylaxis
The AFFINE study achieved its primary objective of 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. Following a single 3e13 vg/kg dose, giroctocogene fitelparvovec demonstrated a statistically significant reduction in mean total ABR compared to the pre-infusion period (1.24 vs 4.73; one-sided p-value=0.0040).
Key secondary endpoints as defined by the trial protocol were met and also demonstrated superiority compared to prophylaxis. 84% of participants maintained FVIII activity >5% at 15 months post-infusion (one-sided p-value = 0.0086) with the majority of participants having FVIII activity ≥15%, and the mean treated ABR showed 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 [15-44 months]; one-sided p-value < 0.0001). Throughout the study, among all dosed participants, one participant (1.3%) returned to prophylaxis post-infusion.
In the AFFINE study, giroctocogene fitelparvovec was generally well tolerated. Transient elevated FVIII levels ≥150% were observed in 49.3% of dosed participants, as measured via chromogenic assay, with no impact on efficacy and safety results. Serious adverse events were reported in 15 patients (20%), including 13 events reported by 10 patients (13.3%) assessed as related to treatment. Treatment-related adverse events generally resolved in response to clinical management.
“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 Professor
Giroctocogene fitelparvovec is a novel, investigational gene therapy that contains a bio-engineered AAV6 capsid and a modified B-domain deleted human coagulation FVIII gene. The goal of this investigational treatment for people living with hemophilia A is that a single infusion of giroctocogene fitelparvovec may allow them to produce FVIII themselves for an extended period of time, providing bleed protection and reducing the need for routine prophylaxis with intravenous (IV) infusions or injections.1,2,3,4
“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
In this Phase 3 study, eligible study participants were initially enrolled in a lead-in study (NCT03587116) and upon successful completion, were enrolled into the AFFINE study where they received a one-time 3e13 vg/kg dose of giroctocogene fitelparvovec by IV infusion. Participants in the AFFINE study were screened with a validated assay designed to identify individuals who test negative for neutralizing antibodies to the gene therapy vector. Clinical study participants will be evaluated in AFFINE over the course of five years, and up to a total of 15 years as part of a long-term follow-up study.
Analyses of the full Phase 3 dataset from the AFFINE study are ongoing and additional data will be presented at upcoming medical meetings. Giroctocogene fitelparvovec has been granted Fast Track and Regenerative Medicine Advanced Therapy designations from the
About the AFFINE Study
The Phase 3 AFFINE (NCT04370054) study is an open-label, multicenter, single-arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in adult male participants (n=75 dosed participants) with moderately severe to severe hemophilia A. Study participants included in the assessments of the key endpoints of the primary efficacy analysis (n=50) completed a minimum six months of routine FVIII replacement prophylaxis therapy during the lead-in study (NCT03587116) providing data to compare with post giroctocogene fitelparvovec treatment.
The primary endpoint measures the total annualized bleeding rate (ABR; spontaneous and traumatic bleedings, treated and untreated) from Week 12 through at least 15 months following treatment with giroctocogene fitelparvovec compared to total ABR on prior FVIII prophylaxis replacement therapy. For more information, visit clinicaltrials.gov.
Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo Therapeutics and
About Hemophilia A
Hemophilia is an inherited, rare bleeding disorder that causes people to bleed for longer than normal due to a deficiency of a protein required for normal blood clotting, known as clotting factor VIII (FVIII) in hemophilia A. The severity of hemophilia is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems.5
Hemophilia A occurs in approximately 25 in every 100,000 male births worldwide.6 Approximately 55-75% of males with hemophilia A have a moderate to severe form of the disease.7 For people who live with hemophilia A, there is an increased risk of spontaneous bleeding as well as bleeding following injuries or surgery.5 It is a lifelong disease that requires constant monitoring and therapy.8
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Disclosure Notice
The information contained in this release is as of
This release contains forward-looking information about giroctocogene fitelparvovec, an investigational gene therapy for hemophilia A, including its potential benefits and topline results from a Phase 3 study, and Pfizer’s hemophilia portfolio, that involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data, including results from the AFFINE study and the long-term follow-up study; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications may be filed in any jurisdictions for any potential indication for giroctocogene fitelparvovec or any other hemophilia product candidates; whether and when any such applications that may be pending or filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether giroctocogene fitelparvovec or any such other product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of giroctocogene fitelparvovec or any such other product candidates; uncertainties regarding the commercial success of Pfizer’s hemophilia products; uncertainties regarding the impact of COVID-19 on our business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended
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1 Ohmori T, Mizukami H, Ozawa K, et al. New approaches to gene and cell therapy for hemophilia. J Thromb Haemost. 2015;13(Suppl 1): S133-142. |
2 Furlan R, Krishnan S, Vietri J. Patient and parent preferences for characteristics of prophylactic treatment in hemophilia. Patient Prefer Adherence. 2015; 9:1687-1694. |
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4 Pfrepper, Christian, et al. "Emicizumab for the Treatment of Acquired Hemophilia A: Consensus Recommendations from the |
5 Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd Edition; 2020. Haemophilia, 26(S6), 1–158. |
6 Iorio A, Stonebraker JS, Chambost H, et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med 2019;171(8):540-546. |
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8 Brod M, Bushnell DM, Neergaard JS, et al. Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM). J Patient Rep Outcomes. 2023;7(1):17. |
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