Bayer HealthCare  has filed a Biologics Licence Application (BLA) to the US Food and Drug Administration (US FDA) seeking approval for BAY 81-8973, a recombinant Factor VIII (rFVIII) compound, for the treatment of haemophilia A in adults and children. BAY 81-8973 is a full-length recombinant factor VIII which has demonstrated clinical evidence of efficacy when used in standard dosage for prophylaxis two times or three times per week. The submission follows Bayer’s recent application to the European Medicines Agency (EMA) for approval of the same indication in the European Union. Bayer plans to submit BAY 81-8973 for approval in other countries in the coming weeks and months.

“Data from our comprehensive clinical program LEOPOLD suggest that BAY 81-8973 could become an important new treatment option for people with haemophilia A”, said Dr. Joerg Moeller, Member of the Bayer HealthCare executive committee and Head of Global Development. “We are committed to improve the lives of people with haemophilia A, and will continue to invest in research and development for innovative treatments.”

The submission was based on positive results from three phase III trials in adults, adolescents and children including a total of 204 subjects. The LEOPOLD II clinical trial demonstrated the superiority of prophylaxis versus on-demand therapy with BAY 81-8973. Results show a 93.3 percent reduction in median annualised bleeding rate (ABR) in the two-times-per-week prophylaxis arm versus on-demand and a 96.7 percent reduction in the three-times-per-week arm versus on-demand. Patients in this study were randomised across the three treatment arms. The actual median ABRs observed were four bleeds when treated two times per week and two bleeds when treated three times versus 60 in the on-demand group. Patients treated in both the two-times-per-week arm and the three-times-per-week arm maintained adequate bleed control while using 20 to 40 IU/KG. When used on-demand, 95 percent of bleeds were controlled with one or two infusions. Overall no clinically relevant treatment-related adverse events occurred and no inhibitor formation was observed. In the pediatric trial including 51 pre-treated children <12 years of age, BAY 81-8973 demonstrated good efficacy with two or three times per week or every other day prophylaxis regimens, and no inhibitors were observed. A further clinical study in previously untreated patients is ongoing. Bayer presented the LEOPOLD II results at the World Federation of Haemophilia (WFH) 2014 World Congress in May 2014.

The LEOPOLD (Long-Term Efficacy Open-Label Programme in Severe Hemophilia A Disease) Clinical Development Program consists of 3 multinational clinical trials designed to evaluate the pharmacokinetics, efficacy, and safety of BAY 81-8973 in subjects with severe haemophilia A (<1 per cent FVIII:C)

LEOPOLD I is a randomised, open-label, crossover study in males aged 12-65 years. The objectives were to demonstrate the efficacy and safety of BAY 81-8973 when used as prophylaxis, for the treatment of bleeding episodes, and for maintaining hemostasis during surgery. LEOPOLD II is a randomised, cross-over, open-label trial also in male subjects aged 12 to 65 years. In this Phase III study, 80 subjects were randomized to receive BAY 81-8973 either as a low-dose prophylaxis regimen (20-30 IU/kg; n=28) two-times-per-week, high-dose prophylaxis (30-40 IU/kg; n=31) three-times-per-week, or on-demand (n=21). The primary objective was to demonstrate the superiority of prophylaxis versus on-demand therapy, with the primary endpoint being bleeding frequency at 12 months. LEOPOLD Kids is an open-label, non-randomised phase III study to evaluate the efficacy and safety of BAY 81-8973 for prophylaxis, treatment of bleeds, and surgical management in previously treated children ?12 years of age.

Haemophilia A, also known as factor VIII deficiency or classic haemophilia is a largely inherited bleeding disorder in which one of the proteins needed to form blood clots in the body is missing or reduced. Haemophilia A, the most common type of haemophilia, is caused by deficient or defective blood coagulation proteins, known as Factor VIII. Haemophilia A is characterised by prolonged or spontaneous bleeding, especially into the muscles, joints or internal organs.