BioMarin Pharmaceutical announced the U.S. Food and Drug Administration (FDA) granted valoctocogene roxaparvovec (formerly BMN 270) Breakthrough Therapy Designation. The FDA's Breakthrough Therapy Designation program is intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious condition. To qualify for Breakthrough Therapy Designation, preliminary clinical evidence must show that that the drug may demonstrate substantial improvement over existing therapies. BioMarin expects to initiate enrollment of a global Phase 3 program before the end of the year.
"The news of the FDA granting Breakthrough Therapy Designation coupled with EU PRIME designation granted in early 2017 by EMA, demonstrates the strong support of global health authorities for valoctocogene roxaparvovec and its expedited development and registration pathway," said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin. "There is a tremendous need to achieve normal steady state Factor VIII levels to eliminate spontaneous bleeding, to avoid the complications of suboptimally corrected bleeding disorder, to improve quality of life and enable patients to live to their fullest potential."
Breakthrough Therapy Designation status was granted based on the data from an ongoing BioMarin Phase 1/2 study, which evaluated safety and efficacy of valoctocogene roxaparvovec. Interim results of the study were provided at the company's R&D Day for investors last week.
The global Phase 3 program includes two studies with valoctocogene roxaparvovec, one with the 4e13 vg/kg dose and one with the 6e13 vg/kg dose. The studies will each likely include approximately 40 patients. In addition, the Company has commissioned its commercial gene therapy manufacturing facility to supply both clinical and commercial drug.
Earlier this month, the company announced that the FDA completed its review of the IND application for valoctocogene roxaparvovec and concluded that it can proceed. The IND application included 52-week data at the 6e13 vg/kg dose and the protocol for the Phase 3 study using the 6e13 vg/kg dose. The protocol for the second Phase 3 study using the 4e13 vg/kg dose has also been submitted to the FDA. Both studies may now begin in the US, following approval from institutional review boards.
Phase 3 Clinical Trial Applications have also been approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for both study protocols, one for the 6e13 vg/kg and one for the 4e13 vg/kg.
The European Medicines Agency (EMA) has granted access to its Priority Medicines (PRIME) regulatory initiative for valoctocogene roxaparvovec. To be accepted into PRIME, an investigational therapy has to show its potential to benefit patients with unmet medical needs based on early clinical data. PRIME focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients with no treatment options. These medicines are considered priority medicines within the European Union (EU).
Hemophilia A, also called Factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. As an X-linked disorder, hemophilia A mostly affects males, occurring in approximately 1 in 5,000 male births. People living with the disease are not able to form blood clots efficiently and are at risk for excessive bleeding from modest injuries, potentially endangering their life. People with severe hemophilia often bleed spontaneously into their muscles or joints. The standard of care for the 43% of hemophilia A patients who are severely affected, is a prophylactic regimen of Factor VIII infusions three times per week. Even with prophylactic regimens, many patients still experience microbleeds and spontaneous bleeding events that result in progressive joint damage.