BioMarin Reports Case of Cancer in Hemophilia Gene Therapy Trial


BioMarin Pharmaceutical, a California-based biotech company, said a patient in a clinical trial of its hemophilia gene therapy Roctavian had developed leukemia, although tests suggest the case may be of natural origin. .

Genetic testing of diseased blood cells showed that a majority of them had a mutation known to be associated with the specific type of leukemia, B-cell acute lymphoblastic leukemia, BioMarin said in a regulatory filing Monday. Meanwhile, further testing indicated that diseased blood cells had low levels of roctavian vector DNA, indicating that genetic material is not being copied when new cells grow, the company added.

Further testing should indicate whether the vector DNA has integrated into the genome of diseased cells, according to BioMarin.

The executives notified the Food and Drug Administration as well as other global regulators of the leukemia case, and none of them called for a halt to ongoing clinical trials, the company said. Additionally, independent safety data monitors also did not call for a pause in testing.

News of the leukemia case comes three weeks after Roctavian was approved in Europe and ahead of BioMarin’s plans to file a new application in the United States. In August 2020, the agency rejected BioMarin’s initial submission because it wanted longer follow-up data from patients treated with gene therapy.

Cases of cancer in clinical trials of many experimental drugs have raised concerns, while in gene therapy they have come under particularly intense scrutiny from US regulators. Many gene therapies, like Roctavian, use adeno-associated viruses to deliver corrective genes to cells, and cases of cancer have been seen in mouse studies using these types of viruses.

The leukemia case was the second case of cancer reported in a patient treated in a clinical trial with Roctavian, also known as valoctocogene roxaparvovec or valrox. Earlier this year, BioMarin reported that a patient treated five years earlier had been diagnosed with a salivary gland tumor, which, based on genomic analysis, was also determined to be unrelated to gene therapy.

BioMarin said in its filing on Monday that the cancer rate among trial participants “appears consistent with expected cancer rates in people with hemophilia.”

Roctavian works by delivering a gene into cells that helps stimulate the production of the clotting protein called factor VIII, which is missing in patients with haemophilia A. In Europe, regulators have approved it for patients with very low levels of factor VIII and BioMarin set a list price of approximately $1.5 million per patient.

BioMarin justifies the price by citing data suggesting that these patients can stop or reduce infusions of a synthetic factor VIII.


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