BioMarin Pharmaceutical, a United States biotech company based in California, reported a leukemia case where a patient from its clinical trial of hemophilia gene therapy Roctavian (also known as volrox or valoctocogene roxaparvovec), developed cancer. However, testing suggests that it could have been naturally caused and not due to the therapy.
The contaminated blood cells were tested and the results revealed a mutation in most of the cells. The mutation found is linked with a certain type of leukemia called B-cell acute lymphoblastic leukemia, revealed BioMarin on Monday. The company also said that further testing on the cells showed low levels of Roctavin vector DNA in the diseased blood cells, which means that the genetic material is not replicating with the growth of new cells. The company also said that more testing should reveal if the vector DNA has unified with the genome of the diseased cells.
Executives informed the FDA (Food and Drug Administration) and other universal regulators about the case of leukemia, however, according to the company, none of the regulators have ordered for the currently underway clinical trials to be put on hold. Independent safety data monitors have also not called for the clinical trials to be paused.
Just three weeks following the approval of Roctavian in Europe came the news of the leukemia case. This could also disrupt BioMarin’s plan to file an application in the United States. The initial approach made by BioMarin was rejected by the agency back in August 2020, claiming that more follow-up data from gene therapy treated patients was required.
Many concerns have been raised surrounding the clinical trials of numerous experimental drugs, however, gene therapy has seen very close inquiry from regulators in the United States. A lot of gene therapies use adeno-associated viruses, just like the Roctavin, to carry corrective genes to the cells. Such types of viruses have revealed cancer cases in mice studies.
Bluebird Bio stopped the sales of its gene therapy called Zynteglo in Europe following two cases of blood cancer during its phase 1/2 trial for sickle cell disease. The drug was designed to mitigate the risk of cancer by combining its own gene with the genome of the human. European regulators later discovered that Zynteglo did not cause the cancer cases.
This was the second case of cancer revealed in a patient treated with Roctavian in a clinical trial. Earlier in the year, the company informed that a patient who had been treated half a decade earlier, had a salivary gland tumor diagnosis and after genomic analysis, it was deemed not connected to gene therapy. BioMarin stated on Monday that the rate of cancer in the participants of the trial seems to be consistent with the expected cancer rates in people with hemophilia.
Roctavian carries a gene into cells that aid the production of Factor VIII, which is a clotting protein. This protein is absent in patients with hemophilia A. It was approved by European regulators for people who have very less Factor VIII levels. BioMarin has set a very high list price per patient of $1.5M. The company justifies the price by signifying that it can reduce or even stop the infusions of Factor VIII.
