BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today positive interim results of an open-label Phase 1/2 study of BMN 270, an investigational gene therapy treatment for severe hemophilia A at the XXXII International Congress of the World Federation of Hemophilia (WFH). The data was presented in the Late Breaking Gene Therapy session by John Pasi, Professor of Haemostasis and Thrombosis, Barts and the London School of Medicine, Honorary Consultant Haematologist, The Royal London Hospital, and a lead investigator of the study. The data presented at the congress is an update since the Company reported initial results on this same study on April 20, 2016. To access the data presented at the Congress, click here.
A total of nine patients with severe hemophilia A received a single dose of BMN 270, seven of whom have been treated at the highest dose of 6 x 1013 vg/kg. As of the July 6 data cut off, post-treatment follow-up ranges from 12 to 28 weeks. For the seven patients treated with the high dose, as of each patients’ most recent reading, six of seven patients had Factor VIII levels above 50%, as a percentage calculated based on the numbers of International Units per deciliter of plasma (IU/dL), and the seventh was above 10%. In addition, four patients who have been followed the longest had a mean Factor VIII level of 146% at their 20 week visit. Two patients with Factor VIII levels above 200% had no unexpected events or need for medical intervention. For the seven patients at the high dose, the median annualized bleeding rate measured from day of gene transfer to data cut of observation period fell to 5 from 20.
No clinically relevant sustained rises in ALT levels or other markers of liver toxicity have been observed. The maximum ALT levels were between 23 and 82 U/L (less than two times the upper limit of normal, which is 43 U/L for the central laboratory in this study) approximately 12 weeks after gene delivery and generally declined over the next few weeks. ALT rises have not been associated with any decrease in Factor VIII levels. A steroid regimen administered to all high dose patients has been well-tolerated. Patients are successfully tapering off of steroids with two subjects off steroid therapy for up to 2.5 weeks with no adverse impact on Factor VIII expression or ALT levels. Study medication was generally well tolerated. No serious adverse events were observed, and most common adverse events were mild in severity.
“These data provide strong proof of concept evidence that restoration of clotting function may be achieved by gene therapy,” said John Pasi, Ph.D. F.R.C.P, 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. “For the first time, patients have reason to hope to avoid bleeding and the opportunity to live a normal life.”
“We look forward to collaborating with experts and health authorities to design the next phase of investigation,” said Hank Fuchs, M.D., Chief Medical Officer at BioMarin. “Beginning in mid-2017, a Phase 2b study will seek to evaluate the optimal dose of BMN 270 using Factor VIII expression as the primary endpoint with material from the to-be-commercialized manufacturing process. If successful, this study could support an accelerated approval given the severe unmet need, the substantial effect and tolerability of the treatment.”
Phase 1/2 Study Design
The current Phase 1/2 study is evaluating the safety and efficacy of BMN 270 gene therapy in up to 12 patients with severe hemophilia A, as defined by the WFH as less than 1% of blood clotting factor. The primary endpoints are to assess the safety of a single intravenous administration of a recombinant AAV vector coding for human-coagulation factor VIII and to determine the change from baseline of factor VIII expression level at 16 weeks after infusion. The kinetics, duration and magnitude of AAV-mediated factor VIII activity in individuals with hemophilia A will be determined and correlated to an appropriate BMN 270 dose.
This is a dose escalation study with the goal of observing an increase in factor VIII levels. Secondary endpoints include assessing the impact of BMN 270 on the frequency of factor VIII replacement therapy, the number of bleeding episodes requiring treatment and any potential immune responses. Patients will be monitored for safety and durability of effect for five years.
Apr 03, 2017 0