Regulatory Decision Summary for Altuviiio

The purpose of this New Drug Submission (NDS) was to seek marketing authorization for Altuviiio (efanesoctocog alfa), a long-acting recombinant antihemophilic factor (coagulation FVIII) with high sustained FVIII activity, indicated in adults and children with hemophilia A (congenital FVIII deficiency) for:

•Routine prophylaxis to reduce the frequency of bleeding episodes

•On-demand treatment and control of bleeding episodes

•Perioperative management of bleeding.

After review of the data submitted, the indication recommended for authorization was:

Altuviiio (Antihemophilic Factor VIII (Recombinant, B-Domain deleted), Fc-VWF-XTEN fusion protein) is indicated in adults, adolescents and children with hemophilia A (congenital Factor VIII [FVIII] deficiency) for:

•Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

•Treatment and control of bleeding episodes

•Perioperative management of bleeding (surgical prophylaxis).

Altuviiio is not indicated for the treatment of von Willebrand’s disease

A single-arm pivotal study, Study EFC16293 (XTEND-1), evaluated the safety and efficacy of a once weekly intravenous injection of a novel factor VIII (FVIII) replacement therapy, Altuviiio, in 133 previously treated adolescent (12 to < 18 years of age) and adult (≥ 18 years of age) hemophilia A patients with severe disease (< 1% of normal FVIII activity). Of the 133 patients enrolled on study, 128 patients had at least 26 weeks of exposure to Altuviiio and were included in the primary efficacy evaluation set. The primary endpoint was the mean annualized bleeding rate (ABR) for treated bleeds compared to historical bleeding data. The key secondary endpoint was an intra-patient comparative analysis for a subset of patients (n = 78) with documented ABRs on prior FVIII prophylaxis compared to the ABRs reported following Altuviiio prophylaxis. A supportive clinical study in 74 children (< 12 years of age) was conducted and the results were consistent with the safety and efficacy of Altuviiio in adolescents and adults, and the non-clinical package included in the NDS supports Altuviiio as a FVIII replacement product for the treatment of hemophilia A.

Routine prophylaxis with Altuviiio resulted in a mean ABR (95% confidence interval [CI]) for treated bleeds of 0.7 (0.5, 1.0) in adolescent and adult patients with severe hemophilia A, with 82 of the 128 patients experiencing no bleeding episodes and 92 of the 128 patients experiencing no joint bleeds. For the key secondary endpoint, an intra-subject comparison (n = 78) demonstrated a 77% in reduction in the ABR for treated bleeds (95% CI: 58%, 87%) during routine prophylaxis with Altuviiio compared to pre-study prophylaxis with available FVIII therapies.

The safety of Altuviiio is consistent with other FVIII replacement therapies. The main risks are hypersensitivity reactions during and following the intravenous injections, the potential for thromboembolic events and the loss of efficacy due to the development of alloantibodies (inhibitors) against the infused FVIII product. These risks are detailed in Product Monograph including that 3 thromboembolic events were reported in patients treated with Altuviiio who had pre-existing risk factors. The Product Monograph was also updated during the review to identify that it was not possible to document inhibitor development following Altuviiio treatment as only previously treated patients were enrolled in clinical studies.

The risk management plan (RMP) was reviewed and the risk mitigation measures proposed in the RMP were considered acceptable for routine pharmacovigilance activities of Altuviiio.

The Quality information submitted for Altuviiio has demonstrated that the Drug Substance and Drug Product can be consistently manufactured to meet the approved specifications.

The Package labels, Package Insert and Brand Name information submitted for AltuVIIIo met all applicable regulations and guidance.

Overall, the benefit-risk profile was favourable for Altuviiio for the approved indication when used under the conditions of use in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Altuviiio, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.