Pfizer Announces Positive Topline Results From Phase 3 Study of Hemophilia A Gene Therapy Candidate
Pfizer (NYSE: PFE) announced positive topline results from the Phase 3 AFFINE study evaluating giroctocogene fitelparvovec, a gene therapy for hemophilia A. The study met its primary objective of non-inferiority and superiority in total annualized bleeding rate (ABR) compared to routine Factor VIII replacement prophylaxis. Key findings include:
- Significant reduction in mean total ABR (1.24 vs 4.73)
- 84% of participants maintained FVIII activity >5% at 15 months post-infusion
- 98.3% reduction in mean treated ABR (4.08 to 0.07)
- Generally well-tolerated safety profile
Pfizer plans to discuss these data with regulatory authorities and advance the therapy to address the treatment burden for hemophilia A patients.
Pfizer (NYSE: PFE) ha annunciato risultati positivi preliminari dallo studio di Fase 3 AFFINE che valuta giroctocogene fitelparvovec, una terapia genica per emofilia A. Lo studio ha raggiunto il suo obiettivo primario di non inferiorità e superiorità nel tasso totale annualizzato di sanguinamento (ABR) rispetto alla profilassi di sostituzione della Fattore VIII di routine. I risultati chiave includono:
- Riduzione significativa della media totale ABR (1.24 contro 4.73)
- L'84% dei partecipanti ha mantenuto l'attività FVIII >5% a 15 mesi dopo l'infusione
- Riduzione del 98,3% nella media ABR trattata (da 4.08 a 0.07)
- Profilo di sicurezza generalmente ben tollerato
Pfizer prevede di discutere questi dati con le autorità regolatorie e di portare avanti la terapia per affrontare il carico del trattamento per i pazienti con emofilia A.
Pfizer (NYSE: PFE) anunció resultados preliminares positivos del estudio de Fase 3 AFFINE que evalúa giroctocogene fitelparvovec, una terapia génica para hemofilia A. El estudio alcanzó su objetivo primario de no inferioridad y superioridad en la tasa total anualizada de sangrado (ABR) en comparación con la profilaxis de reemplazo de Factor VIII de rutina. Los hallazgos clave incluyen:
- Reducción significativa en la media total ABR (1.24 frente a 4.73)
- El 84% de los participantes mantuvo la actividad FVIII >5% a los 15 meses después de la infusión
- Reducción del 98.3% en la media ABR tratada (de 4.08 a 0.07)
- Perfil de seguridad generalmente bien tolerado
Pfizer planea discutir estos datos con las autoridades reguladoras y avanzar en la terapia para abordar la carga del tratamiento de los pacientes con hemofilia A.
화이자(Pfizer) (NYSE: PFE)는 긍정적인 초기 결과를 발표했습니다. 이는 혈우병 A에 대한 유전자 요법인 지로크토코겐 피텔파르보벡을 평가하는 3상 AFFINE 연구에서 나온 것입니다. 이 연구는 일상적인 VIII인자 대체 예방요법에 비해 비열등성과 우월성을 달성하며 총 연간 출혈률(ABR)의 주요 목표를 충족했습니다. 주요 발견 사항은 다음과 같습니다:
- 평균 총 ABR의 유의미한 감소 (1.24 대 4.73)
- 참가자의 84%가 주입 후 15개월 동안 FVIII 활성을 >5% 유지
- 치료된 ABR의 평균이 98.3% 감소 (4.08에서 0.07로)
- 일반적으로 잘 견딜 수 있는 안전성 프로필
화이자는 이 데이터를 규제 당국과 논의하고 혈우병 A 환자들을 위한 치료 부담을 줄이기 위한 요법을 진행할 계획입니다.
Pfizer (NYSE: PFE) a annoncé des résultats préliminaires positifs de l'étude de Phase 3 AFFINE évaluant giroctocogene fitelparvovec, une thérapie génique pour l'hémophilie A. L'étude a atteint son objectif principal de non-infériorité et de supériorité dans le taux annuel de saignement total (ABR) par rapport à la prophylaxie de remplacement par le facteur VIII de routine. Les principales découvertes incluent :
- Réduction significative de l'ABR total moyen (1,24 contre 4,73)
- 84 % des participants ont maintenu une activité FVIII >5 % à 15 mois après l'infusion
- Réduction de 98,3 % de l'ABR moyen traité (de 4,08 à 0,07)
- Profil de sécurité généralement bien toléré
Pfizer prévoit de discuter de ces données avec les autorités réglementaires et de faire avancer la thérapie afin de répondre à la charge de traitement des patients atteints d'hémophilie A.
Pfizer (NYSE: PFE) hat positive erste Ergebnisse aus der Phase-3-Studie AFFINE bekannt gegeben, die giroctocogene fitelparvovec, eine Gentherapie für Hämophilie A, bewertet. Die Studie erreichte ihr primäres Ziel der Nicht-Unterlegenheit und Überlegenheit in der jährlichen Gesamtblutungsrate (ABR) im Vergleich zur routinemäßigen Prophylaxe mit Faktor VIII. Zu den wichtigsten Ergebnissen gehören:
- Signifikante Reduktion der durchschnittlichen Gesamt-ABR (1,24 vs. 4,73)
- 84 % der Teilnehmer hielten die FVIII-Aktivität >5 % nach 15 Monaten nach der Infusion
- 98,3 % Reduktion der durchschnittlichen behandelten ABR (von 4,08 auf 0,07)
- Allgemein gut verträgliches Sicherheitsprofil
Pfizer plant, diese Daten mit den Aufsichtsbehörden zu erörtern und die Therapie voranzutreiben, um die Behandlungsbelastung für Hämophilie A-Patienten zu verringern.
- Phase 3 AFFINE study met primary and key secondary objectives
- Significant 98.3% reduction in mean treated ABR from 4.08 to 0.07
- 84% of participants maintained FVIII activity >5% at 15 months post-infusion
- Only 1.3% of participants returned to prophylaxis post-infusion
- Giroctocogene fitelparvovec granted Fast Track and Regenerative Medicine Advanced Therapy designations by FDA
- Serious adverse events reported in 20% of patients, with 13.3% assessed as treatment-related
- Transient elevated FVIII levels ≥150% observed in 49.3% of dosed participants
Pfizer's announcement of positive topline results from the Phase 3 AFFINE study marks a significant milestone for their gene therapy candidate, giroctocogene fitelparvovec. This investigational therapy demonstrated superiority over traditional Factor VIII (FVIII) prophylaxis in reducing annualized bleeding rates (ABR) in patients with severe hemophilia A. The results showed an impressive
The positive results from the AFFINE study could have substantial financial implications for Pfizer shareholders. The demonstrated efficacy and safety of giroctocogene fitelparvovec place Pfizer at a competitive advantage in the gene therapy market for hemophilia A—a space with few effective long-term treatment options. This advancement, coupled with Fast Track and Regenerative Medicine Advanced Therapy designations, enhances the likelihood of regulatory approval, potentially accelerating the time-to-market. This could lead to significant revenue growth, given the high price points typically associated with gene therapies. Additionally, Pfizer's recent FDA approval for BEQVEZ (hemophilia B gene therapy) suggests a strong pipeline in the hemophilia space, further solidifying their market position. However, investors should remain cognizant of the long-term follow-up required and the competitive landscape.
From a market perspective, the successful Phase 3 results of giroctocogene fitelparvovec could disrupt the current hemophilia A treatment landscape. The ability to provide sustained bleed protection with a single infusion addresses a significant unmet need, potentially shifting patient preference away from frequent prophylactic treatments. This innovation could capture a substantial market share, especially given the high compliance burden of current treatments. The regulatory designations and positive trial results also improve the therapy's marketability and acceptance among healthcare providers and patients. Moreover, as gene therapy becomes more mainstream, we could see increased investor interest and higher valuations for companies leading in this space. Pfizer's strategic positioning with multiple gene therapies under development could enhance their portfolio strength and market dominance.
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.
In the AFFINE study, giroctocogene fitelparvovec was generally well tolerated. Transient elevated FVIII levels ≥
“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 Andrew Leavitt M.D., AFFINE lead investigator, Departments of Laboratory Medicine and Medicine Division of Hematology/Oncology Director, Adult Hemophilia Treatment Center, University of
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 James Rusnak, M.D., Ph.D., Senior Vice President, 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, building on Pfizer’s more than 40-year effort to advance hemophilia treatment.”
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
Pfizer recently received FDA approval for BEQVEZ™ (fidanocogene elaparvovec), its hemophilia B gene therapy. BEQVEZ is also approved in
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 Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug application to Pfizer. Under the agreement, Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization of giroctocogene fitelparvovec.
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
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Disclosure Notice
The information contained in this release is as of July 24, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
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 December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the
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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. |
3 Centers for Disease Control and Prevention. What is hemophilia? October 2023. Available at: https://www.cdc.gov/ncbddd/hemophilia/facts.html#:~:text=Hemophilia%20is%20usually%20an%20inherited,can%20help%20to%20stop%20bleeding. Last accessed: July 2024. |
4 Pfrepper, Christian, et al. "Emicizumab for the Treatment of Acquired Hemophilia A: Consensus Recommendations from the GTH-AHA Working Group." Hämostaseologie (2023). |
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. |
7 WFH. World Federation of Hemophilia Report on the Annual Global Survey 2022. October 2023. (https://www1.wfh.org/publications/files/pdf-2399.pdf). |
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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