Latest News in Hemophilia Gene Therapy for Bleeding Disorders Awareness Month


In observance of Bleeding Disorders Awareness Month, held annually in March, catch up on some of the latest news in gene therapies for hemophilia—one of the most common of these disorders.

In recent months, CGTLive has covered several news and clinical trial data updates on the various gene therapies currently in development for the treatment of hemophilia A and hemophilia B, which are among the most commonly occurring bleeding disorders. According to the National Organization for Rare Disorders, hemophilia B occurs in approximately 1 in every 25,000 male births, slightly less prevalent than hemophilia A, which occurs in approximately 1 in 5000 male births.1

For Bleeding Disorders Awareness Month, which is observed annually in the month of March, the CGTLive team has gathered some of our latest coverage of hemophilia gene therapies below to offer a snapshot at some of the therapeutic progress being made for these rare disorders.

FDA Extends Val-Rox PDUFA Date in Hemophilia A

This month, following the submission of a 3-year data analysis from the ongoing GENEr8-1 clinical trial (NCT03370913), the FDA informed Biomarin that it has extended the review of valoctocogene roxaparvovec (val-rox; Roctavian) for the treatment of severe hemophilia A.2

Considered a major amendment to its application—and thus prompting the extension of the review period—the data from the phase 3 study account for the longest and largest evaluation of a gene therapy in hemophilia to date. Hank Fuchs, MD, president of Worldwide Research and Development of BioMarin, said in a statement at the time that the data enhance the company's application "and further reinforce our belief that Roctavian has the potential to fundamentally transform care for people with hemophilia A.”

Hemgenix Approved in EU for Hemophilia B

Earlier in 2023, in late February, etranacogene dezaparvovec (Hemgenix; CSL Behring) was approved by the European Commission for the treatment of severe and moderately severe hemophilia B in adults without a history of Factor IX inhibitors.3 It was approved for the same indication in the United States in December 2022.

The EC’s decision follows the Committee for Medicinal Products for Human Use’s positive opinion in December 2022 and is based on continued positive data generated by the phase 3 HOPE-B trial (NCT03569891). The trial had previously met its primary end point of reduction in annualized bleeding rate (ABR) post treatment compared with baseline factor IX (FIX) prophylactic therapy.

At the time, Bill Messanotte, MD, the head of research & development and chief medical officer at CSL, called the approval the "essence of great science delivering a medicine that we believe can transform the treatment paradigm."

Fidanacogene Elaparvovec Bests Standard of Care in Phase 3 Hemophilia B Study

Treatment with a single infusion of fidanacogene elaparvovec (PF-06838435) demonstrated noninferiority and even superiority in annualized bleeding rates compared with FIX treatment for patients with moderately severe to severe hemophilia B, according to findings from the phase 3 BENEGENE-2 study (NCT03861273) that were announced by Pfizer in late December 2022, the company developing the gene therapy.4

Prior to administration of fidanacogene elaparvovec in the single-arm BENEGENE-2 study, ABRs with FIX therapy were assessed during a lead in period that lasted 6 months or longer. This lead-in was completed in a separate trial (NCT03587116). In the lead-in period, the ABR with standard of care FIX was 4.43 compared with an ABR of 1.3 from week 12 through 15 months with fidanacogene elaparvovec. This was equivalent to a 71% reduction in ABR, which was significantly superior to standard FIX therapy (P <.0001).

SPK-8011 Yields Durable FVIII Expression in Hemophilia A

Earlier in December 2022, the adenoassociated virus gene therapy SPK-8011 (Spark Therapeutics) demonstrated durable expression of factor 8 (FVIII) in patients with hemophilia A in participants enrolled in a phase 1/2 trial (NCT03003533).5 Most participants with at least 1 year of follow-up maintained FVIII expression within mild hemophilia range. With a median efficacy follow-up of 172.1 weeks (range, 2-285), ABR decreased significantly after treatment with SPK-8011, with an 82% reduction in participants on prior prophylaxis (95% CI, 55-93) and a 99% reduction for participants with prior on-demand treatment (95% CI, 98-100).

Stacy Croteau, MD, MMS, the medical director of Boston Hemophilia Center and an assistant professor of pediatrics at Harvard Medical School, who presented the data at the 64th American Society of Hematology (ASH) Annual Meeting, noted, “As we consider the progress in gene therapy as a hemophilia therapeutic, it’s important to keep in mind 4 key pillars: safety, efficacy, predictability, and durability... The goals and design of [SPK-8011] were to target the lowest effective dose to minimize risk of liver toxicity and anti-capsid immune response while achieving durable expression following single vector administration.”

ICER Suggests $2.9 Million Cap for Hemophilia Gene Therapies

Finally, in November 2022, the Institute for Clinical and Economic Review (ICER) concluded that the price of val-rox should be capped at $1.9 million and the price of EtranaDez should be capped at $2.9 million.6 ICER gave EtranaDez a B+ score for “moderate certainty” of a small or substantial health benefit and “high certainty” of at least a small net health benefit compared with factor IX prophylaxis.

David Rind, MD, chief medical officer of ICER, said in a statement at the time that, "new gene therapies can result in successfully-treated patients appearing ‘cured’ for at least a period of time. During this period these gene therapies will eliminate the need for expensive prophylactic treatment. However, the duration of this ‘cure’ and the safety of therapies remain important uncertainties. At least with val-rox, patients will eventually return to needing prophylaxis.”7

1. Shapiro AD. Hemophilia B. National Organization for Rare Disorders (NORD) website. Updated February 13, 2023. Accessed March 9, 2023.
2. BioMarin Provides Update on FDA Review of Roctavian (Valoctocogene Roxaparvovec) Gene Therapy for Adults with Severe Hemophilia A. News release. Biomarin. March 6, 2023.
3. First Gene Therapy for Hemophilia B, CSL's HEMGENIX®, Approved by the European Commission. News release. CSL Behring. February 20, 2023. Accessed March 9, 2023.
4. Pfizer Announces Positive Top-Line Results from Phase 3 Study of Hemophilia B Gene Therapy Candidate. News release. Pfizer. December 29, 2023. Accessed March 9, 2023.
5. Long-term durable FVIII expression with improvements in bleeding rates following AAV-mediated FVIII gene transfer for hemophilia A: Multiyear follow-up on the phase I/II trial of SPK-8011. Presented at: 64th ASH Annual Meeting, December 10-13, 2022. Abstract #783
6. ICER Publishes Evidence Report on Gene Therapies for Hemophilia A and B. News release. ICER. November 3, 2022. Accessed March 9, 2023.
7. ICER Publishes Evidence Report on Gene Therapies for Hemophilia A and B. News release. ICER. November 3, 2022. Accessed March 9, 2023.
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