Val-Rox up for Review in Hemophilia A 2 Years After Initial BLA Submission


The PDUFA target date is set for March 31, 2023.

The FDA has accepted BioMarin’s resubmitted biologics license application (BLA) for valoctocogene roxaparvovec (val-rox) for review in treating severe hemophilia A.1

The FDA has set a Prescription Drug User Fee Act (PDUFA) target date of March 31, 2023. Val-rox would be the first gene therapy for treating severe hemophilia A to come to market if approved. The FDA has not announced any plans to hold an advisory committee meeting.

"This BLA resubmission is an important step that brings us closer to delivering a gene therapy treatment choice to address the unmet needs of people with severe hemophilia A in the United States. We'd like to extend our sincere gratitude to the bleeding disorders community, study participants, and investigators who have been an integral part of this journey with BioMarin. We look forward to working closely with the Agency on our application for this potentially transformative therapy," Hank Fuchs, MD,president, worldwide research and development, BioMarin, said in a statement.1

BioMarin previously resubmitted the val-rox BLA to the FDA in September 2022 after collecting 2-year follow-up data and additional durability and safety data as requested after the FDA rejected the BLA submission in August 2020 and delayed resubmission in June 2022.2,3 Meanwhile, in the EU, val-rox was approved by the European Commission with conditional marketing authorization in August 2022.4

READ MORE: BioMarin to Investigate B-ALL Case in Val-Rox Gene Therapy Clinical Trial

"In this application, we have provided a substantial body of evidence that supports the safe and effective use of val-rox for the treatment of adults with severe hemophilia A. In addition, we have proposed 15 years of follow-up for all clinical study participants, as well as a post-approval registry study to follow patients dosed in a real-world setting, to further characterize long-term effects on safety and efficacy that will contribute to increasing the body of knowledge of AAV gene therapy in severe hemophilia A. While we recognize the potential for the Agency to extend the PDUFA action date to review additional long-term follow up data, we are pleased the FDA has initiated its review of the BLA without requesting additional data,” Fuchs added.1

BioMarin’s resubmitted BLA included data from the 2-year results of the GENEr8-1 phase 3 study (NCT03370913) and additional 5-year follow-up data from an on-going phase 1/2 dose-escalation study (NCT02576795).2 Patients treated with val-rox in the global GENEr8-1 clinical trial showed stable and durable bleed control and reductions in both mean annualized bleeding rate and mean annualized Factor VIII infusion rate. Included in the BLA is a proposed long-term extension study for all treated participants in the program to be followed-up for 15 years as well as a post-approval, registry, real-world study.

Val-rox administered in a single 6x1013 vg/kg dose has continued to be well-tolerated without delayed-onset treatment related adverse events (AEs). Common treatment-related AEs include transient infusion associated reactions, mild to moderate rises in liver enzymes without long-lasting clinical sequelae, and alanine aminotransferase elevations. Other AEs include aspartate aminotransferase elevations n = 101; 63%), nausea (n = 55; 34%), headache (n = 54; 34%), and fatigue (n = 44; 28%). No participants have developed inhibitors to Factor VIII, thromboembolic events or malignancy associated with val-rox treatment. BioMarin is currently investigating a case of B-cell acute lymphoblastic leukemia in a patient treated in the GENEr8-1 study, with no changes to study protocol announced.5

"This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile. We remain committed to sharing these data with the public, along with even longer-term data generated through our ongoing clinical trials and any post-approval studies, to further our understanding of AAV gene therapy in severe hemophilia A and of gene therapies more broadly,” Fuchs said in a previous statement.2

Val-rox is also being evaluated for the same indication in an open-label, single-arm phase 3 study with prophylactic corticosteroids (Study 270-303; NCT04323098), a phase 1/2 Study in people with pre-existing AAV5 antibodies (Study 270-203; NCT03520712) and a phase 1/2 study in people with active or prior factor VIII inhibitors (Study 270-205; NCT04684940).1

1. FDA accepts BioMarin's biologics license application (BLA) for valoctocogeneroxaparvovec AAV gene therapy for adults with severe hemophilia A. News release. BioMarin. October 12, 2022.
2. Biomarin resubmits biologics license application (BLA) for valoctocogeneroxaparvovec AAV gene therapy for severe hemophilia A to the FDA. News release. BioMarin Pharmaceutical Inc. September 29, 2022.
3. BioMarin delays hemophilia a therapy valoctocogeneroxaparvovec filing as FDA calls for more data. News release. BioMarin. May 31, 2022.
4. First gene therapy for adults with severe hemophilia A, BioMarin's ROCTAVIAN™ (valoctocogeneroxaparvovec), approved by European Commission (EC). News release. BioMarin. August 24, 2022.,-BioMarins-ROCTAVIAN-TM-valoctocogene-roxaparvovec-,-Approved-by-European-Commission-EC
5. Securities and Exchange Commission, Form 8-K. BioMarin Pharmaceuticals. September 12, 2022. Accessed September 14, 2022.
Recent Videos
Manali Kamdar, MD, on The Importance of Bringing Liso-Cel to Earlier Lines of Lymphoma Treatment
Manali Kamdar, MD, on Acclimating to Routine CAR T Practice in the Field
Manali Kamdar, MD, on Evaluating Liso-Cel in Mantle Cell Lymphoma by Lines of Therapy, Prior BTKi
Mark Walters, MD
Manali Kamdar, MD, on Bringing Liso-Cel to Earlier Lines of Treatment
Sowmya Viswanathan, PhD, on Translating Cell Therapies to the Clinic at ISCT 2024
Omar Nadeem, MD, on Initial Efficacy of GPRC5D-CAR in R/R Multiple Myeloma
Omer A. Abdul Hamid, MD, on Improving Gene Therapy’s Effect and Accessibility
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Michael Wang, MD, a professor in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center
© 2024 MJH Life Sciences

All rights reserved.