FDA Accepts BLA For Bayer's Proposed Hemophilia A Treatment

Bayer has announced the FDA’s acceptance of its Biologics License Application (BLA) for BAY94-9027 for the treatment of hemophilia A in adults and adolescents aged 12 years or older.

Hemophilia A is a genetic bleeding disorder caused by insufficient levels of factor VIII, a blood protein clotting factor, and is caused by disruptions or mutations to the F8 gene on the X chromosome. Treatment for the disorder often involves replacing the missing protein with recombinant factor VIII. BAY94-9027 is an extended half-life, site-specifically PEGylated recombinant human factor VIII compound that is designed to prolong factor VIII activity in the blood and preserve coagulation activity. The extended half-life of the therapy may result in reduced frequency of infusions for patients with hemophilia A.

Submission of the BLA is based on results from the PROTECT VIII phase 2 and phase 3 trial. The multinational, partially randomized, open-label trial was conducted in men aged 12 to 65 years. The design of the study allowed patients who demonstrated good bleeding control on twice-weekly dosing to adjust their schedule to longer intervals between infusions, and was intended to reflect a real-world approach to prophylaxis.

A total of 134 patients were treated in the study. After a 10-week run-in period of twice-weekly dosing, patients who had 1 breakthrough bleed or less during the 10-week period were randomized to receive BAY94-9027 every 5 days or every 7 days for 26 weeks. Patients who had more than 1 such bleed remained on twice-weekly dosing. The primary efficacy assessment was the annualized bleeding rate (ABR), or the annualized number of total bleeds. The median ABRs for the 3 groups during the 26-week period were follows:

• Twice-weekly treatment: 4.1 (range, 2.0 to 10.6)
• Every-5-day treatment: 1.0 (range, 0.0 to 2.0)
• Every-7-day treatment: 3.9 (range, 0.0 to 6.5)

The researchers concluded that the prolonged half-life of the investigational drug provided prevention of bleeding at dose intervals up to every 7 days, that effective prophylaxis was also demonstrated at dosing every 5 days or twice weekly, and that dosing can be tailored to individual patients’ needs. BAY94-9027 was also effective in treating bleeds, with approximately 90% of bleeds controlled with 2 or fewer infusions of the drug. BAY94-9027 was well tolerated; none of the patient developed inhibitors to factor VIII during the study period.

"The filing acceptance for BAY94-9027 by the FDA represents a milestone to Bayer in its commitment to seeking potential treatments to address the unmet needs of people living with hemophilia A," said Dario Mirski, MD, senior vice president and head of medical affairs Americas for Bayer. "For more than 25 years, Bayer has been committed to working with the community to support patients and deliver a spectrum of factor VIII products to provide physicians with treatment options for managing their patients with hemophilia A."