HIGH IMPACT – In an SEC filing, BioMarin disclosed that they were notified on August 19th, 2022 that a participant in the Roctavian Phase 3 trial was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). Based on BioMarin’s assessment of the case to date, including initial genetic testing of the leukemic cells, BioMarin believes at this time that this cancer is unrelated to Roctavian.

  • The overall rate of all cancers observed in all Roctavian trial patients (2 in approximately 400 patient years of observation) appears consistent with expected rates of cancer in persons with hemophilia.
  • Testing on leukemic cells enriched to 90% purity from peripheral blood carried negligible levels of Roctavian vector DNA (less than 1 copy per 500 cells). These negligible, near background levels of Roctavian indicate that Roctavian is not clonally expanding in these leukemic cells.
  • Additional genomic analyses are underway, which BioMarin expects to confirm the absence of Roctavian vector integration events contributing to leukemic growth, as well as to provide further insights into the underlying genetic etiology of this case.

inThought Analysis

This is the second known case of a patient treated with Roctavian developing cancer, following a patient in the Phase 1/2 trial who developed a carcinoma. In both these cases, the malignancy was ruled unlikely related to the gene therapy, and the rate of cancer among hemophilia gene therapy patients remains consistent with the rate of cancer among hemophilia patients in general.

There has not been a cancer event attributable to treatment with a hemophilia gene therapy, and this cancer disclosure is not likely to affect the upcoming BLA submission expected by the end of September. However, the risk of vector genome integration leading to cancer remains a concern among physicians and the patient communities for which gene therapies are being developed.


Source: BioMarin Form 8-K