Photo courtesy of Biogen
The European Commission (EC) has approved eftrenonacog alfa (Alprolix) to treat hemophilia B.
This recombinant factor IX Fc fusion protein therapy is indicated for both on-demand and prophylactic treatment in patients of all ages.
Eftrenonacog alfa is developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.
Prophylactically, eftrenonacog alfa can be administered with an initial dose every 7 days or every 10 days, and the dosing interval can be adjusted based on individual response.
Sobi and Biogen are collaborators in the development and commercialization of eftrenonacog alfa for hemophilia B.
Sobi said it is working to make the drug available in Europe as quickly as possible.
The EC’s decision to approve eftrenonacog alfa was based on results from two phase 3 trials: the B-LONG study and the Kids B-LONG study.
B-LONG study
The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.
Patients received eftrenonacog alfa in 1 of 4 treatment arms:
- Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
- Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
- On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
- Perioperative management (n=12, including 8 from arms 1-3).
Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.
The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.
The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.
Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.
The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.
One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.
Kids B-LONG
In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.
Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.
Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.
None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.
None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa treatment.
The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.
