Opportunity to take part in a hemophilia B gene therapy trial

Hamilton, January 22, 2024 – McMaster University, in collaboration with CSL Behring, has announced a new gene therapy trial for etranacogene dezaparvovec (Hemgenix) in hemophilia B.

Hemgenix received its Notice of Compliance (marketing approval) from Health Canada in November 2023 (see reference below). It was previously approved by both the U.S. Food and Drug Administration and the European Medicines Agency. However, Hemgenix is not yet available in Canada. Gene therapies for hemophilia B are currently at the health technology assessment stage. This will be followed by price negotiations. The Provinces and Territories will then make decisions on whether or not to add them to their drug formularies. It is not known what the outcome will be nor how long this might take.

The trial is a Phase 3b, open-label, multicentre, single dose study investigating the efficacy and safety of CSL222 (etranacogene dezaparvovec) gene therapy administered to adult subjects with severe or moderately severe hemophilia B with detectable pre-treatment AAV5 neutralizing antibodies. Dr. Alfonso Iorio is the principal investigator for the McMaster study site in Canada.

AAV5 (adeno-associated virus, type 5) is the vector that is used to deliver the factor IX gene to the liver. In other licensed gene therapies for hemophilia A and B, people are excluded from receiving the treatment if they test positive for AAV antibodies. However, in the trials for Hemgenix, it was discovered that the therapy was just as effective in people who tested positive (with antibody levels below 1:700) as in those who tested negative. Only one person, who had a very high AAV antibody titer, failed to benefit. So the purpose of this new study is to discover what is the level of AAV5 antibody above which the gene therapy is unlikely to work. Consequently, trial subjects must test positive for the antibody during the screening phase to be eligible.

Overall, approximately 35 study participants with severe or moderately severe hemophilia B who have pre-existing AAV5 antibodies will be enrolled in this study, with at least 10 study participants with a pre-existing AAV5 antibody level of 1:1400 or higher. Study participants will be enrolled in this study from approximately 60 sites around the world.

If you are considering participating in this study, or simply wish to have more information, talk to your hematologist, or reach out directly to the McMaster team: Dr. Alfonso Iorio (iorioa@mcmaster.ca) and Suzanne Bajkor, Research Coordinator (bajkor@mcmaster.ca).

For more information about hemophilia gene therapy, consult the Canadian Hemophilia Society Gene Therapy Education Program (www.hemophilia.ca/gene-therapy). There you will find a comprehensive booklet called All About Hemophilia Gene Therapy, a series of podcasts with world-renowned experts called Hemophilia Gene Therapy: Dream or Reality?, webcasts and much more.

Ref: Hemgenix Health Canada product monograph