Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.
Albutrepenonacog alfa is a fusion protein linking recombinant coagulation factor IX with recombinant albumin.
The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for perioperative management of bleeding.
Albutrepenonacog alfa is being developed by CSL Behring.
The company says the product is the first and only hemophilia B therapy with up to 14-day dosing intervals.
According to CSL Behring, albutrepenonacog alfa can deliver high-level protection from bleeds by maintaining factor IX activity levels at an average of 20% in patients treated prophylactically every 7 days and an average of 12% in patients treated prophylactically every 14 days.
Albutrepenonacog alfa has also been approved in Canada, the European Union, Switzerland, and the US.
Phase 3 trial
The MHLW approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were published in Blood. The study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks, followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
