San Francisco-based drugmaker BioMarin Pharmaceuticals revealed this week that one of the patients participating in its phase 3 study of its hemophilia A gene therapy had been diagnosed with cancer.
The drug, to be sold as Roctavian, uses modified adeno-associated viruses — called AAV5 — to deliver a copy of the F8 gene, which holds the instructions cells need in order to produce clotting factors that are absent in patients with the disorder. According to the recent SEC filing, the trial patient was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL).
The trial has included 270 trial patients, and BioMarin says that the overall rate of cancer reported appears consistent with expected rates of cancer in hemophilia patients. Complying with regulatory requirements, BioMarin says it began a comprehensive assessment of the case which included genetic testing performed at the site. Among the findings, BioMarin reported that the leukemic cells carried a chromosomal translocation that is a known driver mutation in leukemia, and that the cells carried negligible levels of the AAV vector DNA.
Although Roctavian was recently approved by the European Commission, its approval journey in the United States has been a bit bumpy. The FDA first granted Breakthrough Therapy Designation for the drug in 2017, but when BioMarin submitted its Biologics License Application, the agency sent a Complete Response Letter its way, recommending that the company completed the Phase 3 Study and later submitted two-year follow-up safety and efficacy data on all study participants. In March of 2021, the FDA granted Roctavian Regenerative Medicine Advanced Therapy (RMAT) designation.