Etranacogene Dezaparvovec Approval May Pave Way for Val-Rox in Hemophilia A


The FDA has decided not to hold an advisory committee meeting for Roctavian after all.

BioMarin’s biologics license application (BLA) review for its adeno-associated virus gene therapy valoctocogene roxaparvovec (val-rox; Roctavian) may not be so delayed after all, as the company announced that the FDA will no longer be holding an advisory committee meeting to discuss the therapy’s benefit in hemophilia A.1 The FDA will still complete the scheduled pre-licensure inspection of BioMarin’s gene therapy manufacturing facility in Canada.

"The review of a BLA is a dynamic process, and we appreciate FDA's ongoing engagement as we work toward delivering a potentially transformative treatment choice to those patients with severe hemophilia A," Hank Fuchs, MD, President, Worldwide Research and Development, BioMarin, said in a statement."We look forward to further dialogue with the Agency as it reviews our application."

Earlier in November, BioMarin disclosed that val-rox's PDUFA target action date may be delayed if the FDA deems the submission of new data from a phase 3 analysis as a major amendment to the application.2 The current PDUFA date is March 31, 2023. The FDA had requested the submission of expected 3-year data from on the ongoing phase 3 GENEr8-1 clinical trial (NCT03370913).

“The FDA stated that these data are expected to provide longer-term efficacy and safety information and would thus be useful to people with Hemophilia A and healthcare providers in making better and more informed decisions when considering val-rox as a treatment choice should it be approved, "Fuchs said in an earlier statement.2

READ MORE: ICER Suggests $2.9 Million Cap for Hemophilia Gene Therapies

The FDA accepted BioMarin's resubmitted BLA for val-rox in October 2022, following marketing authorization by the European Commission in August 2022. The gene therapy has received RMAT, breakthrough therapy, and orphan drug designations from the FDA.

Full 52-week results from the GENEr8-1 study demonstrated that a single dose of the infused gene therapy resulted in statistically significant increases in endogenous Factor VIII production (<.001) and significantly reduced bleeding events and use of factor VIII concentrate (<.001 for both), all while maintaining a relatively good safety profile (N = 134).3

The announcement about the advisory committee meeting comes a week after UniQure and CSL Behring’s Hemgenix (etranacogene dezaparvovec) became the first approved gene therapy for treating hemophilia B.3 The BLA was supported by positive data from 54 participants with hemophilia B in the pivotal phase 3 HOPE-B trial (NCT03569891).

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” Peter Marks, MD, PhD, director, Center for Biologics Evaluation and Research, FDA, said in the FDA release.“Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

1. BioMarin announces advancements in FDA review of ROCTAVIAN™ (valoctocogeneroxaparvovec) for adults with severe hemophilia A. News release. BioMarin Pharmaceuticals. November 23, 2022.
2. BioMarin Announces Incremental Progress on Biologics License Application (BLA) Review for ValoctocogeneRoxaparvovec AAV Gene Therapy for Adults with Severe Hemophilia A Program. News release. BioMarin Pharmaceutical. November 7, 2022.
3. Ozelo MC, Mahlangu J, Pasi J, et al. Valoctocogeneroxaparvovec gene therapy for hemophilia A. New Eng J Med. 2022; 386: 1013-1025. doi: 10.1056/NEJMoa2113708
4. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022.
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