GENEr8-1 study details and results
The trial was conducted in men 18 and older with severe congenital hemophilia A who had received prophylaxis with factor VIII concentrates for at least 1 year and were negative for factor VIII inhibitors.
The patient sample included 20 men enrolled directly, and 110 participants in a prospective noninterventional study of bleeding episodes, factor VIII infusions, and patient-reported outcomes in individuals with severe hemophilia A.
Participants received one infusion of valoctocogene roxaparvovec, at a dose of 6x1013 vector genomes per kilogram of body weight.
They remained on factor VIII prophylaxis for 4 weeks after the infusion of the gene therapy product, but after that factor VIII was used on an as-needed basis.
A total of 134 patients received an infusion and were included in the safety analysis. Two patients who were HIV positive were excluded from the modified intention-to-treat efficacy analysis.
As noted above, the trial met its primary efficacy endpoint of change from baseline in factor VIII activity 49-52 weeks after infusion, and the secondary endpoints of change from baseline to after week 4 in annualized use of factor VIII concentrate and the annualized number of treated bleeding episodes.
The most common adverse event was an elevation in alanine aminotransferase levels, the investigators noted.
These elevations in ALT levels, which have also been seen with gene therapy for hemophilia B, occurred in 85.8% of patients and could be safely managed with immunosuppressants, the authors commented.
Other common adverse events were headache, nausea, and elevations in aspartate aminotransferase levels, each occurring in slightly more than one third of patients.
“Overall, the risk-benefit profile appears favorable,” the team commented.
The study was supported by BioMarin Pharmaceutical. Dr. Ozelo disclosed grant support from the company. Dr. Thornburg disclosed serving as a consultant to BioMarin and others.
A version of this article first appeared on Medscape.com.