RFVIIIFc: Phase III data
Top-line data from the open-label, international Phase III A-LONG trial in 165 previously treated male hemophilia A patients aged 12 and older showed that rFVIIIFc as prophylaxis met the primary efficacy and safety endpoints. To meet the efficacy endpoint, the partners said rFVIIIFc as prophylaxis needed to reduce annualized bleeding rates by >=50% compared to on-demand treatment with rFVIIIFc. Biogen Idec did not disclose the reduction in bleeding rates, but did report that rFVIIIFc led to overall median annualized bleeding rates, including spontaneous and traumatic bleeds, of 3.6 in the weekly prophylaxis arm and 1.6 in the individualized prophylaxis arm vs. 33.6 in the on-demand episodic treatment arm. rFVIIIFc was generally well tolerated with no inhibitors to rFVIIIFc detected and no cases of anaphylaxis or serious adverse events reported. According to the study design, the trial would have been stopped if 2 inhibitors to rFVIIIFc were detected.
The most common adverse events, occurring outside of the perioperative management arm, were nasopharyngitis, arthralgia, headache and upper respiratory infection. Additionally, 98% of bleeding episodes were controlled by 1 or 2 injections of rFVIIIFc. In a subgroup of 9 patients undergoing surgical procedures who received rFVIIIFc as perioperative management, the treating physicians rated the hemostatic efficacy of rFVIIIFc as "excellent" or "good" in 100% of surgeries. Furthermore, a pharmacokinetic analysis in a protocol-defined subset of patients showed that the approximate terminal half-life of rFVIIIFc was 19 hours vs. 12.4 hours for Advate octocog alfa. ...