Baxter International has presented additional efficacy and safety data from the phase III pivotal study of BAX 855, an investigational, extended half-life recombinant factor VIII (rFVIII) treatment for hemophilia A based on ADVATE [Antihemophilic Factor (Recombinant)].
The new data expand on the previously disclosed topline results from the pivotal trial, which found that BAX 855 met the study's primary endpoint in the control and prevention of bleeding episodes and routine prophylaxis. Patients in the twice-weekly prophylaxis arm of the trial experienced a 95% reduction in median annualized bleed rate (ABR) as compared to those in the on-demand arm (1.9 v. 41.5, respectively). The study findings supported Baxter's December 2014 submission for approval of BAX 855 to the FDA.
"These pivotal trial results provide evidence to support the efficacy profile of BAX 855 in controlling, preventing or reducing the frequency of bleeding episodes when administered prophylactically twice weekly. Our goal with BAX 855 is to extend the interval between infusions while maintaining a similar efficacy profile to ADVATE," said John Orloff, M.D., vice president and global head of research and development for Baxter BioScience.
The prospective, global, multi-center, open-label, two-arm phase III study evaluated BAX 855 among 137 previously treated hemophilia A patients (PTP) who were 12 years or older. Patients were assigned either to twice weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-50 IU/kg, n=17).
In addition to a reduced ABR, BAX 855 also was effective in treating bleeding episodes, 96% of which were controlled with one or two infusions at a median dose of 29 IU/kg per infusion. Treatment was rated excellent or good for nearly all episodes (96.2%). In the prophylactic group (n=101), 40% of patients experienced no bleeds. The study also showed that BAX 855 pharmacokinetics offered a 1.4-1.5-fold extended half-life compared to 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, were reported. Seven adverse reactions in six patients, including headache, diarrhea, nausea and flushing were reported.
Baxter's continuation study for patients who completed the pivotal trial and the phase III study among previously treated patients under the age of 12 with severe hemophilia A remain ongoing. Upon completion of the pediatric study, Baxter 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 15 years in a number of approved medicines that treat chronic or serious conditions.