The Australian Therapeutic Goods Administration has approved albutrepenonacog alfa (Idelvion) to treat hemophilia B patients of all ages.
Albutrepenonacog alfa is a fusion protein linking recombinant coagulation factor IX with recombinant albumin.
The product is now approved in Australia for use as routine prophylaxis to prevent and reduce the frequency of bleeding, for on-demand control of bleeding, and for perioperative management of
bleeding.
Albutrepenonacog alfa has also been approved in Canada, the European Union, Japan, Switzerland, and the US.
Albutrepenonacog alfa is being developed by CSL Behring.
The company says albutrepenonacog alfa is the first and only Australian-registered factor IX therapy that delivers high-level protection from bleeding with up to 14-day dosing for appropriate patients.
According to CSL Behring, albutrepenonacog alfa can deliver high-level protection 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.
“The Australian Haemophilia Centre Directors’ Organisation (AHCDO) views the development of effective long-acting clotting factor concentrates as a major step forward in the management of our patients with hemophilia,” said Simon McRae, MMBS, consultant hematologist and chairman of AHCDO.
“The ability to maintain clotting factor levels above a level that prevent the vast majority of bleeding events with less frequent infusions has the potential to improve long-term outcomes in individuals with hemophilia.”
Phase 3 trial
The Therapeutic Goods Administration 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.
“I have seen first-hand the benefits Idelvion has had on children with hemophilia B,” said PROLONG-9FP investigator Julie Curtin, MBBS, PhD, of The Children’s Hospital at Westmead in New South Wales.
“Idelvion has enabled children on regular treatment with factor IX to reduce the frequency of infusions without increasing their risk of bleeding. For a child to only need an injection every 1-2 weeks is a good step forward in the management of hemophilia B, which I welcome, and I am sure my patients will welcome this improvement too.”
