BioMarin Pharmaceutical will add an additional Phase 3 study to the clinical development of its investigational gene therapy BMN 270 for hemophilia A. BioMarin will conduct two separate trials testing the effectiveness and safety of two different doses of BMN 270. Both trials are expected to initiate in the fourth quarter of 2017.
This decision was based on positive results from the ongoing open-label Phase 1/2 study that were presented during the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress in Berlin, Germany.
The presentation was titled “Interim results of an open-label, Phase 1/2 study of BMN 270, an AAV5-FVIII gene transfer in severe haemophilia A.”
BMN 270 is a gene therapy designed specifically to deliver the correct form of the faulty gene that causes hemophilia A. This strategy will potentially allow the normal production of the missing clotting Factor VIII, representing a possible cure for those patients.
Fifteen patients were included in the Phase 1/2 trial (NCT02576795). The patients received four different doses of BMN 270. Six patients received a single 4e13 vg/kg dose administrated intravenously, and seven patients received a 6e13 vg/kg dose. The remaining patients received lower doses of the potential therapy.
Results from three patients who received 4e13 vg/kg dose reached, or are near, the normal ranger of Factor VIII activity levels, after 32 weeks of treatment. The other three patients who received the same dose completed 20 weeks upon BMN 270 administration with change of Factor VIII activity levels from severe to mild, showing tendency to improve even further in two patients. This dose of BMN 270 reduced the mean annualized bleed rate of the patients by 92 percent, and the mean annualized Factor VIII infusions were reduced by 97 percent.
All who received the highest dose (6e13 vg/kg) presented mean levels of Factor VIII within normal range upon 20 weeks post-treatment follow-up. After one year these patients still presented mean Factor VIII levels of more than 50 percent.
“We now plan to move forward as rapidly as possible with two separate Phase 3 studies with the 4e13 vg/kg and the 6e13 vg/kg doses. By concurrently moving both of these doses into Phase 3 development, we have the opportunity to determine if patients may be better served by having one or both of these doses commercially available,” Hank Fuchs, MD, president of Worldwide Research and Development at BioMarin, said in a press release. “Given the low level of pre-existing immunity to AAV5 [the vector that delivers the Factor VIII gene], we expect that approximately 90 percent of patients would be treatment candidates for BMN 270 based on this criteria,” Fuchs said.
Based on these positive results, BioMarin is going to further test these two BMN 270 dosages, 4e13 vg/kg and 6e13 vg/kg, in Phase 3 studies. Each of the trials is expected to include about 100 patients with severe hemophilia A. However, the trial’s final design is not yet established.
In February the European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to BMN 270, which is expected to expedite its development and regulatory review.