News and Expert Insights in Hemophilia Gene Therapy for Bleeding Disorders Awareness Month 2025
In observance of Bleeding Disorders Awareness Month, held annually in March, catch up on some of the latest news and expert insights in gene therapy for hemophilia, which is among the most common of these disorders.
According to the National Organization for Rare Disorders, hemophilia A and hemophilia B are among the most commonly occurring bleeding disorders.1 Hemophilia B occurs in approximately 1 in every 25,000 male births, and is thus slightly less prevalent than hemophilia A, which occurs in approximately 1 in 5,000 male births.
For Bleeding Disorders Awareness Month, which is observed annually in the month of March, the CGTLive® team has gathered some of our recent coverage of hemophilia gene therapies from the past few months below to offer a snapshot at some of the happenings related to therapies for these disorders. A notable trend has been the scaling back of production or discontinuation of approved products for these indications, but research and development of new products also remains ongoing. Click the "READ MORE" buttons for more details and information about each item.
Pfizer Jettisons FDA-Approved Hemophilia B Gene Therapy Beqvez
February 21, 2025 — 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.
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. 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.
Evaluating siRNA Therapy Fitusiran in Combination With Antithrombin Modulation for Hemophilia
December 19, 2024 — At at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California, Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, presented data from the ATLAS-OLE clinical trial (NCT03754790) assessing fitusiran, an siRNA therapeutic targeting antithrombin, as prophylaxis in combination with appropriate bleed management guidelines for management of breakthrough bleeding in people with hemophilia A and hemophilia B. CGTLive®'s sister site HCPLive® sat down with Pipe at the conference to learn more.
Pipe explained the relevant background information behind the study and went over the key results. He concluded that fitusiran is a highly effective prophylactic agent and provides a better patient experience.
Immunogenicity Outcomes for Val-Rox Reported From Phase 3 GENEr8-1 Study
August 24, 2024 — Data from the phase 3 open-label trial GENEr8-1 (NCT03370913) suggest that treatment with valoctocogene roxaparvovec (Roctavian; BioMarin) resulted in immune responses that were mainly directed toward the AAV5 capsid, with every participant All seroconverted to AAV5 total binding antibody (TAb) and AAV5 transduction inhibitor (TI) positive by 8 weeks post dose. Additionally, these titers were not associated with affects on Factor VIII (FVIII) activity nor alanine aminotransferase (ALT) elevations.
Colloquially known as val-rox, the gene therapy was the first approved for treatment of adults with severe hemophilia A, defined as congenital factor VIII (FVIII) deficiency with FVIII activity of less than 1 IU/dL who do not have antibodies to AAV5 according to an FDA-approved test. The agency gave the go-ahead based on data from GENEr8-1, the labeling of which includes the prospective data from 112 patients in whom 6-month baseline ABR was collected, who reported a mean ABR reduction of 52% (2.6 bleeds per year) through the end of follow-up (median, 3 years) compared with baseline ABR while receiving routine FVIII prophylaxis (5.4 bleeds per year).
Study author Brian R. Long, PhD, MS, a principal scientist in clinical immunology at BioMarin Pharmaceutical, and colleagues noted that none of the 134 men included in the study developed a FVIII inhibitor response that proved meaningful. “Of the 4 participants who had a single positive FVIII inhibitor response before or after valoctocogene roxaparvovec administration, 1 instance was a confirmed false positive, and the remaining 3 were isolated and transient,” they noted, adding that in the 9% of patients with FVIII TAb-positive results, cases were “transient and had low titers, consistent with previous reports” from populations of both people with hemophilia A and healthy donors that do not progress to become inhibitors.
Uptake of Nononcology Gene Therapy Remains Slow in Hematology
August 19, 2024 — Uptake of hemophilia gene therapies has also been slow. Although BioMarin’s val-rox 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. Just this month, BioMarin announced that it will be scaling back its efforts with regard to val-rox, with the company now mainly focusing 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. UniQure and CSL Behring’s hemophilia B gene therapy, etranacogene dezaparvovec (marketed as Hemgenix), which was approved by the FDA in November 2022, has also been slow to be embraced by patients.
“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 earlier in 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.”
BioMarin Limits Geographic Scope of its Plans for Hemophilia A Gene Therapy
August 10, 2024 — BioMarin has announced that it will be scaling back its efforts with regard to valoctocogene roxaparvovec (val-rox, marketed as Roctavian), its gene therapy product for the treatment of adults with severe hemophilia A.
Going forward, the company is mainly focused 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. In addition, because sufficient supply of the gene therapy product has already been produced for the time being, BioMarin has put a pause on the manufacturing of val-rox. Furthermore, the company is not planning to enroll new patients in clinical trials for the gene therapy, although patients who have previously been treated in trials will continue to receive support and be monitored for long-term outcomes.
"We continue to believe that ROCTAVIAN is an important option for people with severe hemophilia A, offering the potential for years of bleed control after a single, one-time treatment," Alexander Hardy, MBA, the president and chief executive officer of BioMarin, said in a statement. "By rightsizing our resourcing, we are creating a path for Roctavian to contribute to our profitability while still providing full support to patients. We are deeply grateful to the hemophilia community and to the patients and healthcare providers who participated in our clinical trials, and we will continue to provide support, as well as to meet our regulatory commitments for ongoing monitoring."
