Jan 9, 2017

BioMarin Pharmaceutical, Inc., recently reported positive updates to their ongoing phase 1/2 clinical study of BMN 270, the company’s hemophilia A gene therapy. These interim results will be presented at the 35th Annual J.P. Morgan Healthcare Conference, January 9-13, 2017, in San Francisco, CA.

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 trial, the recruitment for which is still ongoing, is to evaluate the safety and efficacy of BMN 270 in up to 15 individuals with severe hemophilia A. To date, a total of nine patients have received a single dose of the therapy and seven of those have been treated at the highest dose. As of the December 9, 2016, data cutoff, post-therapy patient follow-up ranges from 34 to 50 weeks.

Data based on each patient’s most recent reading showed that six of seven patients in the high- dose group continue to have FVIII levels above 50%, while the seventh continues to be more than 15%. These percentages effectively shift these patients’ FVIII severity levels from severe (less than 1%), to mild (5%-40%) or normal (50%-150%). 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.

For the six patients at the high dose and previously on a FVIII prophylactic treatment regimen, the mean annualized bleeding rate (ABR) dropped 91% from 16.3 before receiving BMN 270 to 1.5 two weeks after receiving the therapy. For those same six patients, the mean annualized FVIII infusions fell 98% from 136.7 to 2.9.

In addition, six of the seven patients in the high-dose group are within the normal alanine aminotransferase (ALT) range, and one patient is less than 5% above the upper limit of normal. ALT tests help screen for elevated enzyme levels in the blood and subsequent adverse effects on liver function. Some of the early trial patients did experience elevated ATL levels, therefore investigators initially decided to administer prophylactic corticosteroids (steroid hormones) to all the patients. Patients successfully tapered off of steroids with no lasting significant impact on FVIII expression or ALT levels. The requirement for prophylactic corticosteroids has been since removed for all newly enrolled patients in the study.

“These data continue to show promising evidence that restoration of clotting function can be achieved by gene therapy,” said John Pasi, PhD, FRCP, Professor of Haemostasis and Thrombosis at Barts and the London School of Medicine and Dentistry. He is the primary investigator for the BMN 270 Phase 1/2 clinical trial. “The increase in Factor VIII levels we have seen has the potential to stop patients' bleeding and has changed how we think about treating hemophilia. For the first time we can truly start considering the opportunity for our patients to live a more normal life.”

Source: BioMarin press release dated January 8, 2017

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