VIDEO: Practicing hematologists should prepare for paradigm shift in treatment
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ORLANDO, Fla. — In this video at the ASH Annual Meeting and Exposition, Steven W. Pipe, MD, professor of pediatrics and pathology at the University of Michigan, reviews recent innovations in hemophilia and incorporating gene therapy into practice.
For 5 decades, replacement therapy with factor concentrates was the standard treatment for hemophilia. It is a “high-burden therapy” that requires frequent intravenous injections, according to Pipe. A few years ago, the FDA approved a bispecific humanized monoclonal antibody for hemophilia that has a longer half-life and can be administered subcutaneously.
“Patients on this regimen have very good bleed control and some patients go years at a time without breakthrough bleeding,” Pipe told Healio. “This has set a new bar for what the expectations would be if we were going to think about doing gene therapy for hemophilia.”
Emerging research on gene therapy involving an adeno-associated virus (AAV) with a factor IX transgene revealed durable factor IX expressions in patients with hemophilia B, according to Pipe. Patients who received the treatment experienced substantial reductions in bleeding and factor IX utilization post therapy.
At the ASH Annual Meeting and Exposition, Pipe presented data on a similar AAV treatment strategy that substitutes the native factor IX with a “hyperactive version of factor IX” known as factor IX Padua. In a phase 2b study, the treatment was safe and increased the activity of patients’ factor IX levels to a non-hemophilic rage. These levels were maintained 1-year posttreatment. Investigators are now evaluating the AAV treatment strategy with revised construct in a phase 3 trial for hemophilia B, according to Pipe.
Exciting advances in hemophilia A include the phase 3 development of a factor VIII construct developed by BioMarin, Pipe said. The company submitted a market authorization application for the construct in Europe. The “hopeful” next steps would be for the company to submit a biologic license application to the FDA.
“We could see both a gene therapy for hemophilia A and a gene therapy for hemophilia B sometime over the next 12 to 18 months as commercial entities,” Pipe said. “This is something that has really got to get us moving at the treatment center level because we need to learn how to prepare our patients [and] how to talk to them about this completely new paradigm of treating hemophilia. ... I think is going to be clearly transformative for a lot of patients’ lives.”
Reference:
Pipe S, et al. Abstract 3348. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando, Florida.
Disclosure: Pipe reports being a consultant for Apcintex, Bayer, BioMarin, Catalyst Bioscience, CSL Behring, Freeline, HEMA Biologics, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Shire, Spark Therapeutics and uniQure.