Gene therapy in hemophilia featured heavily at the World Federation of Hemophilia Global Forum held in Montréal November 13 to 14, 2019. Glenn Pierce, MD, PhD, WFH Vice President, Medical, said several advances have enabled therapeutic success for factor VIII and factor IX gene therapy. These include improvements in the design, manufacturing, and production of vectors (the delivery mechanism for gene therapy) and the use of higher vector doses.
There has been an explosion of clinical and preclinical research activity in this area in recent years. Several phase 3 clinical trials are underway, with many more gene therapy products in earlier stages of trials. Demonstrating the effectiveness and safety of a gene therapy product in a phase 3 study is a prerequisite for submission to a regulatory body, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).
Andrea Laslop, Head, Austrian Federal Office for Safety in Health Care, said, “The EMA assigns priority review (PRIME designation) to promising new treatments expected to become gamechangers.” The scheme is dedicated to reinforcing scientific and regulatory advice, establishing early interactions among stakeholders, optimizing the generation of robust data, and enabling the accelerated assessment of marketing applications to the EMA.
BioMarin Pharmaceuticals was the first to receive PRIME designation for its investigational gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A. BioMarin submitted its application for marketing authorization to the EMA in November, 2019 with review expected to begin in January, 2020. PRIME designation shortens the review process from 210 to 150 days.
Submission of the first gene therapy product for regulatory approval is an exciting milestone for the hemophilia community. However, much work remains to be done to optimize manufacturing and laboratory testing, to understand the variability in the factor levels expressed, and to monitor long-term safety and efficacy outcomes. “It would be good to be able to tell the person with hemophilia what factor level to expect,” said Pierce.
Pierce also reported on the second WFH Gene Therapy Round Table, an event established in 2018 to better understand the challenges and opportunities that gene therapy will bring to the hemophilia community. Hosted annually by the WFH in Montreal, invited delegates discuss topics such as how to collect long-term safety and efficacy data, how to finance gene therapy, and how to achieve global access to this technology. The third meeting will be held in March, 2020; a great deal of discussion is anticipated given the recent and ongoing advances in gene therapy research for hemophilia.
The first regulatory submission of a gene therapy product can be considered an early chapter in the book on novel treatments for hemophilia. This space will evolve as long-term data on safety and effectiveness are gathered.
For further background information on Gene Therapy for Hemophilia, visit the WFH eLearning Platform.