Pfizer Jettisons FDA-Approved Hemophilia B Gene Therapy Beqvez

Pfizer has made the decision to discontinue development and commercialization of fidanacogene elaparvovec (Beqvez), an FDA-approved adeno-associated virus (AAV) vector-based gene therapy for the treatment of hemophilia B.¹

According to a statement from a Pfizer spokesperson given to Fierce Pharma, the company made the decision based on a lack of interest from the patient and clinician communities. It was pointed out that no patients had received the gene therapy in the commercial setting. Notably, with the dropping of Beqvez, Pfizer currently has no gene therapy products on the market or in development.

Beqvez was approved by the FDA on April 26, 2024, for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid determined by an FDA-approved test.² At the time, it was announced that the therapy would be priced at $3.5 million. The biologics license application for the gene therapy was supported by data from the phase 3 BENEGENE-2 clinical trial (NCT03861273) that assessed fidanacogene elaparvovec against the standard of care (SOC) FIX prophylaxis replacement regimen in 45 individuals with hemophilia B.

Updated safety data from BENEGENE-2 was recently presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California.³ CGTLive®'s sister site, HCPLive®, sat down with Samelson-Jones at the conference to learn more. He provided an overview of the safety findings, noting 5 serious adverse events (SAEs) of gastrointestinal (GI) ulcers and associated bleeding and anemia that occurred in 2 participants, and pointed out that these SAEs were probably secondary to steroids that were prescribed without gastric protection, emphasizing the importance of GI protection during steroid use following gene therapy.

“It should be very reassuring that there's nothing unexpected," Samelson-Jones told HCPLive. “I think the story of AAV-based gene therapy for hemophilia over the last 3 decades has been surprises. And I think what this is should be reassuring, that there's nothing has popped up that it that is of concern.”

Notably, uptake of hemophilia gene therapy products by the patient community has been slow in general.^4-6 For example, although BioMarin’s valoctocogene roxaparvovec (val-rox, marketed as Roctavian) was approved in June 2023, the first patient outside of clinical trials did not receive val-rox until December 2023, at the Center for Inherited Bleeding Disorders (CIBD) in California.⁵ BioMarin announced in August 2024 that it would be scaling back its efforts with regard to val-rox, with the company mainly to focus on distributing the gene therapy in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed.⁶ UniQure and CSL Behring’s hemophilia B gene therapy, etranacogenedezaparvovec (marketed as Hemgenix), which was approved by the FDA in November 2022, has also been slow to be embraced by patients.⁷

“We haven't seen a lot of patients dosed yet,” Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, told CGTLive regarding Hemegenix in early 2024. “And I don't think that’s related to either the enthusiasm of the clinicians or the patients, but really just the mechanics of how to deliver this in the clinical space, as opposed to the research trials... We've seen that a lot of the hemophilia treatment center sites have got their components together, their infrastructure and personnel so that they can actually start delivering this in the commercial setting. And so, I'm really looking forward to seeing this making a difference in patients' lives in a real world setting.”

REFERENCES
1. Pfizer discontinues hemophilia treatment Beqvez, emptying its gene therapy portfolio. News article. Fierce Pharma. Februay 21, 2025. Accessed February 21, 2025. https://www.fiercepharma.com/pharma/pfizer-empties-gene-therapy-portfolio-discontinues-hemophilia-treatment-beqvez
2. U.S. 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 April 26, 2024. https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B
3. Samelson-Jones B, Frenzel L, Kavakli K, et al. Use of FidanacogeneElaparvovec, a Gene Therapy Vector, to Deliver a Stable, Fully Functional Human Factor IX Transgene for the Treatment of Hemophilia B: A Combined Analysis of Safety. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract #3577
4. Center for Inherited Blood Disorders Administers Country's First Gene Therapy Infusion to Treat Hemophilia A. News release. Center for Inherited Blood Disorders. January 11, 2024. Accessed August 15, 2024. https://firstwordpharma.com/story/5817834?from=article
5. BioMarin Announces Updated Strategy for ROCTAVIAN® to Focus on U.S., Germany and Ital. News release. BioMarin Pharmaceutical Inc. August 5, 2024. Accessed August 15, 2024. https://investors.biomarin.com/news/news-details/2024/BioMarin-Announces-Updated-Strategy-for-ROCTAVIAN-to-Focus-on-U.S.-Germany-and-Italy/default.aspx
6. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed August 15, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b