BioMarin Provides Trial Updates for Hemophilia A Gene Therapy

BioMarin recently announced clinical trial updates relevant to valoctocogene roxaparvovec (formerly known as BMN 270) its investigational gene therapy for the treatment of adults with hemophilia A. The gene therapy program associated with valoctocogene roxaparvovec was originally licensed in February 2013 from the University College London and St. Jude Children’s Research Hospital in Memphis, TN, and has since been developed by BioMarin.

Valoctocogene roxaparvovec uses adeno-associated viruses (AAVs) as vectors to carry the genetic codes that prompt the production of the factor VIII (FVIII) protein that is deficient in people with hemophilia A. AAVs are designed to deliver the genetic material into living cells to sustain therapeutic effect without causing disease or triggering significant immune responses.

While BioMarin’s valoctocogene roxaparvovec clinical development program encompasses six studies, the recent updates focused on two in particular. The first is based on an ongoing phase 1/2 trial in adults with hemophilia A in which participants were placed in two groups, one in which patients received a higher dose and a second group where patients received a lower dose. The results showed significant clinical improvements in annualized bleeding rate (ABR) and use FVIII replacement therapy.

Data also suggested that bleeding was well controlled in the larger dose group as observed through ABR and requisite FVIII infusions. In the year prior to study entry, the mean ABR was 16.3. At three plus years, the ABR was a mean of 0.7, representing an overall ABR reduction of 96%. The company also reported a “continued absence” of target joints and target joint bleeds during the three years observed. In addition, FVIII product usage in the large dose group demonstrated sustained efficacy three years post-administration. Rates of study participants who experienced zero bleeds necessitating FVIII infusions were 71% in the first year and 86% in both the second and third years. Overall, there was a  96% reduction in mean FVIII usage over three years.

The company also reported positive data associated with a lower dose administration of valoctocogene roxaparvovec, which showed “substantial and sustained” reductions in bleeds requiring FVIII infusions. In the year prior to the study, mean ABR was 12.2. At two years post-administration, ABR was a mean of 1.2, representing a 92% reduction.

“With three years of data, it’s clear that valoctocogene roxaparvovec has the potential to change the way we treat this debilitating disease, which can improve the quality of life for people with severe hemophilia A,” said John Pasi, MB, ChB, PhD, from Barts and the London School of Medicine and Dentistry and primary investigator for this Phase 1/2 study. “For people who have had to inject themselves with factor VIII every other day to prevent bleeding, this treatment has the potential to be transformational.”

In a second press release, BioMarin announced that valoctocogene roxaparvovec achieved pre-specified clinical criteria for regulatory review in the U.S. and Europe. The company will meet with the Food and Drug Administration (FDA) and European Medicines Agency (EMA) to review the phase 3 data and the other elements of the submission and intends to announce the timing for its planned marketing applications in the third quarter of 2019. “Reaching this pre-specified clinical endpoint is an important milestone that brings us one step closer to a potential regulatory submission in both the U.S. and Europe for valoctocogene roxaparvovec to treat adults with severe hemophilia A,” said Hank Fuchs, MD, President of Worldwide Research and Development at BioMarin. “Our discussions with the FDA and EMA underscore the high level of unmet need in the hemophilia community, and we look forward to continuing our productive dialogue on the submissions.”

Data will be  presented at the International Society on Thrombosis and Haemostasis Congress in Melbourne, Australia, July 6-10, 2019.

Source: BioMarin press releases dated May 28, 2019