BioMarin Pharmaceutical, Inc. recently provided updated interim results from a phase 1/2 clinical study of BMN 270, the company’s investigational hemophilia A gene therapy. 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. These AAVs are designed to deliver genetic material into living cells to sustain therapeutic effect without causing disease or triggering significant immune responses.
The purpose of the trial is to evaluate the safety and efficacy of BMN 270 in up to 15 individuals with severe hemophilia A. The results were presented at the 26th International Society on Thrombosis and Haemostasis Meeting, July 8-13, 2017, in Berlin, Germany.
Of the 15 participants, seven received a higher dose of BMN 270, while six received a slightly lower dose of the therapy. An additional two patients received the lowest dose, to no therapeutic effect. As of the May 31, 2017 data cutoff, all patients in the higher dose group had reached the one year post-treatment follow-up benchmark. According to a BioMarin press release, FVIII levels from post-treatment weeks 20 through 52 have been consistently within the normal range (between 50%-150%). One year after a single treatment, FVIII levels of the high dose group continue to be above 50%. Notably, once patients in this group reached FVIII levels of above 5%, their mean annualized bleeding rates (ABR) were reduced 97%, from 16.3 to 0.5. In addition, mean annualized FVIII infusions were reduced 94%, from 136.7 to 8.5.
The six patients in the lower dose group also showed positive results. After reaching FVIII levels ranging from 5% to 38% (mild severity) at post treatment weeks 8 through 24, patient mean ABR plummeted from 12.2 to zero. Mean annualized FVIII infusions also dropped from 144.2 to zero. In terms of safety, BioMarin reports that BMN 270 was well tolerated by patients across all doses and that no patients developed inhibitors to FVIII and no one withdrew from the study.
“Patients at the two highest doses have stopped prophylactic treatment and to date, bleeds have effectively been eliminated,” said John Pasi, PhD at Barts and the London School of Medicine and Dentistry and Haemophilia Clinical Director at Barts Health National Health Service Trust and primary investigator for the BMN 270 Phase 1/2 clinical trial. “In addition to the clinical data showing meaningful improvement in bleeds and factor VIII levels up to 52 weeks, the quality of life data from the patients at the highest dose demonstrate that the potential clinical benefit could also represent a tangible improvement in a patient's quality of life.”
BioMarin plans to initiate a phase 3 registrational study for BMN 270 in the fall of 2017.
Source: BioMarin press release dated July 11, 2107
