BioMarin says PhIII gene therapy study participant's cancer is unrelated to therapy
As the FDA has delayed any hope of BioMarin launching its hemophilia A gene therapy until next year at the earliest, the company said in an SEC filing Monday that a participant in one of its Phase III studies for the therapy was diagnosed with a type of cancer known as B-cell acute lymphoblastic leukemia.
After submitting the safety report to FDA, BioMarin said it “believes at this time that this cancer is unrelated” to the treatment, known as valoctocogene roxaparvovec. None of the gene therapy’s ongoing trials have been halted as a result, the company said. On the status of its investigation into this case of B-ALL, BioMarin told investors:
The preliminary results of genetic testing performed at the site revealed that 85% of leukemic cells carried a Philadelphia-like (Ph-like) chromosomal translocation, which is a well-known driver-mutation in leukemic cells. Further, testing on leukemic cells enriched to 90% purity from peripheral blood carried negligible levels of BMN 270 vector DNA (less than 1 copy per 500 cells). These negligible, near background levels of BMN 270 indicate that BMN 270 is not clonally expanding in these leukemic cells. Additional genomic analyses are underway, which BioMarin expects to confirm the absence of BMN 270 vector integration events contributing to leukemic growth, as well as to provide further insights into the underlying genetic etiology of this case.
The announcement comes as Europe recently signed off on the new gene therapy, known commercially as Roctavian, based on the results of a Phase III single-arm, non-randomized study of 134 male patients with hemophilia A without a history of factor VIII inhibitor and without detectable pre-existing antibodies to AAV5.
“Two years after the administration, efficacy data showed that the therapy significantly increased factor VIII activity levels in the majority of patients. Bleeding rates were reduced by 85% and most patients (128) no longer needed factor VIII replacement therapy,” EMA said.
In the US, the FDA issued a CRL for the therapy in 2020, seeking two years of follow-up safety and efficacy data on all study participants. Since the CRL, the FDA has granted a regenerative medicine advanced therapy designation to valoctocogene roxaparvovec, which uses an AAV vector to deliver the gene for factor VIII.
But FDA in May also passed along more information requests, and BioMarin said its BLA resubmission at the time was expected by the end of this month, which is a timeline the company said it still expects to meet.