Baxalta, a global biopharmaceutical provider dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, has published complete data from the phase II/III pivotal study and phase I trial of BAX 855 in Blood, the journal of the American Society of Hematology. BAX 855 is Baxalta’s investigational, extended half-life recombinant factor VIII (rFVIII) treatment for hemophilia A based on ADVATE [Antihemophilic Factor (Recombinant)], a treatment for hemophilia A with more than 11 years of real-world patient experience.
BAX 855 will be marketed in the U.S. under the brand name ADYNOVATE [Antihemophilic Factor (Recombinant), Pegylated] upon approval. The trial assessed the treatment’s safety and efficacy profiles for bleed prevention with a twice-weekly dosing schedule, showing a mean half-life extension of 1.4- to 1.5-fold compared with ADVATE. The positive study results were originally reported in August of 2014 and supported the company’s December 2014 submission for approval of BAX 855 to the FDA.
“ADYNOVATE has the potential to offer an important new option for patients, providing the combination of recognized ADVATE bleed prevention with a simple, twice-weekly dosing schedule,” said Leonard Valentino, M.D., global head, Hematology Medical Affairs, Baxalta. “The results of this pivotal trial demonstrate the ability of ADYNOVATE to help further personalize treatment regimens to minimize the impact that hemophilia has on patients’ lives.”
The prospective, global, multicenter, open-label, two-arm phase II/III study evaluated BAX 855 among 137 previously treated patients (PTP) with hemophilia A aged 12 to 65. Patients were assigned to either twice weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-60 IU/kg, n=17). As previously disclosed, BAX 855 met the study's primary endpoint for the prevention of bleeding episodes and the treatment with prophylaxis compared to on-demand treatment. Patients in the twice-weekly prophylaxis arm of the trial experienced a 95% reduction in median annualized bleed rate (ABR) as compared with those in the on-demand arm (1.9 v. 41.5, respectively). BAX 855 also was effective in treating all bleeding episodes, 95.9% of which were controlled with one or two infusions at a median dose of 29.0 IU/kg per infusion.
Treatment was rated excellent or good for nearly all bleeding episodes (96.1%). In the prophylactic group (n=101), 39.6% of compliant patients experienced no bleeds. The study also showed that BAX 855 pharmacokinetics offered a 1.4 to 1.5-fold mean extended half-life compared with ADVATE with a median infusion interval of 3.6 days, supporting the findings from the phase I trial. No patients developed inhibitors to BAX 855 and no treatment-related serious adverse events, including hypersensitivity reactions, were reported. Seven adverse reactions in six patients, including headache, diarrhea, nausea and flushing were reported.
Baxalta's Continuation Study is ongoing for patients who completed the pivotal trial and the pediatric phase III study among previously treated patients under the age of 12 with severe hemophilia A. This continuation study also is available for patients who have not participated in previous BAX 855 studies. Upon completion of the pediatric study, Baxalta expects to file for marketing authorization with the EMA in 2016.
BAX 855 is based on ADVATE, a full-length FVIII molecule with more than 11 years of real-world patient experience. Through a collaboration with Nektar Therapeutics, BAX 855 leverages proprietary pegylation technology designed to prolong the amount of factor VIII available for use in the body. This proprietary technology has been used for over 15 years in a number of approved medicines that treat chronic or serious conditions.
Baxalta leads the industry with the broadest portfolio of hemophilia treatments, and meets individual therapy choices with a range of options at each treatment stage. As an estimated 70% of people with hemophilia globally remain undiagnosed and untreated or undertreated, Baxalta is focusing on continuing to innovate to address some of the greatest challenges associated with hematologic disorders including hemophilia.