February 4, 2022 – BioMarin’s gene therapy (valoctocogene roxaparvovec) for haemophilia A is currently in development and not yet licensed by regulators. BioMarin has completed dosing 134 patients in its phase 3 clinical study while it also continues to follow up, as recommended by regulators, on 15 patients from its ongoing phase 1/2 clinical study, which completed enrolment in 2017.

At the 2022 EAHAD Congress, BioMarin reported two-year data from its phase 3 study, which will be included in the next EHC novel products newsletter. During this update, speaker Prof Johnny Mahlangu also reported an update from BioMarin’s ongoing phase 1/2 study, namely that in November 2021, a single serious adverse event (SAE) was reported in a patient from this study who had developed a lump in their neck, which was later diagnosed as salivary gland cancer. The cancer was removed and the patient is being monitored. A serious adverse event (SAE) is the term used to describe the occurrence of a serious health issue in a study, regardless of whether that health issue was caused by the treatment under investigation.

The SAE was reviewed by a committee composed of the BioMarin study team, the study investigator, an independent committee of experts that routinely monitors the study (Data Monitoring Committee (DMC)), and other medical and scientific experts, as well as reported to regulators. The SAE is thus far not suspected to be related to valoctocogene roxaparvovec. BioMarin are conducting further analysis of the removed cancer tissue. More details should be reported to the community in the coming months.

On February 4 in parallel to its EAHAD Congress announcement, BioMarin issued a letter to the patient community, which is downloadable here.

This is the third report of cancer in patient participants of a haemophilia gene therapy trial. Cancer was reported in the Hope-B trial where cancer occurred in a male patient with multiple risk factors associated with the development of liver cancer, including a history of hepatitis C (treated prior to enrolment), exposure to hepatitis B virus, evidence of non-alcoholic fatty liver disease, and advanced age. After analysis of a biopsy for integration of the gene therapy delivery system (AAV vector genome) into the cells, no difference was seen between the healthy liver tissue and the liver cancer tissue. Cancer was also reported by Dr Barbara Konkle at the American Society of Haematology, namely in the BAX-335 trial, where the SAE of tonsil cancer was reported as unrelated to gene therapy, and a subsequent biopsy found no integration of AAV vector genome in the tonsil cancer tissue.

Cancer, in general, has been an element of focus for all gene therapies. The EHC, on behalf of its patient community, remains vigilant and insistent on reviewing and examining any and all SAEs in these – like in all – therapies. This will help ensure the safety of these potentially life-changing treatments in the future. Whilst staying vigilant, we must also remain aware of the general background risk of cancer. In addition to the general population risk for some form of cancer, there is also an increased risk of liver cancer, as reported by the European Haemophilia Safety Surveillance System (EUHASS), in those haemophilia patients who have had a history of HIV, Hepatitis C and/or Hepatitis B. The EHC shall continue to request investigators, clinicians, companies and regulators to make every effort to detangle a SAE from a general background risk in the most expedient manner possible so that patients can make decisions about future treatments with all available evidence.

The EHC will continue to monitor and report on further developments.