BioMarin Pharmaceutical Inc. recently announced preliminary data from an ongoing Phase 1/2 clinical trial with BMN 270, the company’s investigational gene therapy for the treatment of individuals with hemophilia A. The gene therapy program associated with BMN 270 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 San Rafael, CA-based BioMarin.
BMN 270 uses adeno-associated viruses (AAVs) as delivery vehicles, or vectors, to carry the genetic codes that prompt the production of the factor VIII (FVIII) protein that is deficient in people with hemophilia A. Ideally, AAVs deliver the genetic material into living cells to sustain therapeutic effect without causing disease or triggering significant immune responses.
The purpose of the phase 1/2 trial, the recruitment for which is still ongoing, is to evaluate the safety and efficacy of BMN 270 in up to 12 individuals with severe hemophilia A. To date, a total of eight patients have received a single dose of the therapy and six of those have been treated at the highest dose. Investigators reported that patients at the highest dose showed rising FVIII activity levels that ranged between 4% and 60%, with five of six of the “high dose” patients now over 5% and two of six at over 50%. All high dose patients saw their hemophilia A severity shift positively from severe (less than 1% FVIII) to the either moderate (1%-5%), mild (5%-40%) or normal (50%-150%) FVIII levels. Even a modest boost in FVIII levels for an individual with hemophilia A can lead to a significant reduction in bleeding complications and have a dramatic impact on quality of life.
Alanine aminotransferase (ALT) tests, which help screen for elevated enzyme levels in the blood and subsequent adverse effects on liver function, are also being employed during the study. Some of the early trial patients did experience elevated ATL levels, therefore investigators decided to administer prophylactic corticosteroids (steroid hormones) to all the patients. To date, no cases of elevated ALT have been reported.
“If BMN 270 allows hemophilia A patients to maintain around 5% of normal levels of factor VIII, it could have a real and meaningful clinical benefit by reducing the need for factor VIII infusions and spontaneous bleeds,” said John Pasi, PhD, FRCP, Professor of Haemostasis and Thrombosis at Barts and the London School of Medicine and Dentistry and primary investigator for the BMN 270 Phase 1/2 clinical trial. “I am looking forward to further assessing the data over the 16 weeks and beyond in this ongoing study.”
According to the BioMarin press release, Phase 3 “design preparation and high volume manufacturing plans” are underway.
Source: BioMarin press release dated April 20, 2016
