BioMarin Investigational Gene Therapy Updates

DNA strand

An update for the hemophilia community from BioMarin regarding a previously reported serious adverse event in the ongoing hemophilia A gene therapy [valoctocogene roxaparvovec, BMN 270] Phase 3 study that was deemed, by the Independent Data Safety Monitoring Committee and the company, very unlikely to be related to the investigational therapy.

Clinical Development Program Update

BioMarin is providing an update to the community regarding our ongoing gene therapy clinical trial program in hemophilia A. BioMarin’s investigational gene therapy for hemophilia A has not been approved for use in the United States; it is in ongoing clinical trials evaluating its safety and efficacy.

BioMarin’s BMN 270, is currently being studied in adults with severe hemophilia A and is under review by the FDA, in the United States.

Serious Adverse Event Reporting Timeline

A serious adverse event (SAE) is the term used to describe the occurrence of a serious health issue in a study participant, regardless of whether it was caused by the treatment under investigation.

On August 19, 2022, BioMarin was notified that a participant in the BMN 270 Phase 3 study (named GENEr8-1) was diagnosed with leukemia. He received the dose of BMN 270 approximately 3 years before. The specific type of cancer was B-cell acute lymphoblastic leukemia (B-ALL). This leukemia is cancer of the bone marrow and blood affecting the type of white blood cells known as B-lymphocytes.

As with any serious adverse event, a committee of experts was brought together to help determine the cause of the leukemia and whether it may be related to the therapy being studied in the trial. The committee was composed of the BioMarin study team, the study investigator, an independent committee of experts that routinely monitors the study (Independent Data Safety Monitoring Committee), as well as other medical and scientific experts.

The study team as well as external experts concluded that, based on the results of initial molecular analysis, presented in October at a scientific congress, that it is very unlikely BMN 270 played a role in the development of B-ALL in this study participant. These initial findings were based on test results for this participant which were consistent with findings typically seen in patients who are diagnosed with B-ALL. The relevant health regulatory authorities were notified.

In November of 2022, BioMarin received the results of additional analyses related to this SAE. The analyses were conducted by a third-party research organizations and show the absence of any AAV vector-host integration into the samples. The assessment supports the previous determination that it is very unlikely that BMN 270 played a role in the development of B-ALL in this study participant and there are currently no plans to change the conduct of ongoing BMN 270 trials. This participant remains in the study and is currently receiving standard-of-care treatment for B-ALL. BioMarin will continue to follow his health for five years after initial treatment, and for another decade as a participant in a long-term follow-up study.

BioMarin has not observed any cancer events that have been determined to be AAV study drug-related in participants in clinical trials of BMN 270.

The safety of patients and study participants is BioMarin’s top priority. Although the evidence so far points to the conclusion that it is very unlikely that BMN 270 played a role in the development of B-ALL in this participant, patients should speak with their physicians about any questions they have about gene therapy.

BioMarin supports the shared decision-making framework to enable a personalized dialogue between individual patients, their family or care partners, physician and healthcare team and we remain committed to informing and educating physicians and other healthcare professionals, patients, advocacy groups and the hemophilia community as we learn more about this case.

We acknowledge and thank the members of this community for their continued commitment and for the huge contribution that they have made to research in hemophilia.

Regulatory Status

On October 12, 2022, BioMarin’s Biologics License Application (BLA) for valoctocogene roxaparvovec was accepted for review by the US FDA with a review action date of March 2023. Subject to completion of the filing review, FDA evaluates data provided by BioMarin and makes its decisions based on their assessment of safety and efficacy.

For additional information:

  • Visit and type in the study code “BMN 270-301”
  • For inquiries or to provide feedback from advocacy organizations, please contact:
  • Contact BioMarin Medical Information at or toll free at 1 –800-983-4587

Past Updates