Regulatory Decision Summary for Alhemo

The purpose of this New Drug Submission (NDS), filed by Novo Nordisk Canada Inc., was to seek marketing authorization under for Alhemo for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors. The submission was reviewed using the international review work sharing model of the Access Consortium.

After evaluation of the submitted data package, Alhemo was authorized for the treatment of adolescent and adult patients (12 years of age or older) with hemophilia A (congenital factor VIII [FVIII] deficiency) who have FVIII inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes. As part of the indication statement, prescribers were informed that there is limited clinical experience of Alhemo use in patients known to have mild or moderate hemophilia.

Marketing authorization for Alhemo was based on the results of a multi-national, multi-centre, open-label, phase 3 trial that investigated the safety and efficacy of Alhemo (concizumab injection) for routine prophylaxis in hemophilia A patients with factor VIII (FVIII) inhibitors and hemophilia B patients with factor IX (FIX) inhibitors who were 12 years of age and older. Patients were randomized 1:2 to receive either on-demand treatment with bypassing agents or daily prophylactic treatment with Alhemo. Given the rare nature of hemophilia patients with inhibitors, a combined clinical study of hemophilia A and B patients with inhibitors was considered acceptable as Alhemo is expected to work in both hemophilia populations as it targets a protein in the extrinsic coagulation pathway.

Efficacy was evaluated when all patients in the on-demand and Alhemo prophylaxis arms had completed at least 24 or 32 weeks, respectively, by comparing the number of treated spontaneous and traumatic bleeding episodes between the treatment arms. Despite issues that arose due to a clinical pause with Alhemo because of thromboembolic risks associated with this therapy, patients treated with Alhemo had a significant reduction in treated bleeds compared to patients who received on-demand therapy with bypassing agents. This was reported as a mean annualized bleed rate of 1.7 for patients treated with Alhemo compared to 11.8 for patients treated with on-demand bypassing agents. This was a statistically significant reduction in bleeding events, which is considered a clinically meaningful benefit of Alhemo.

Key safety concerns of Alhemo are hypersensitivity reactions and thromboembolic events. Risk mitigation measures included in the product monograph are a Serious Warnings and Precautions box for thromboembolic events and considerations on when to use this product and how to monitor for these events. Injections site reactions are the most common adverse reactions reported for Alhemo, including injection site pruritus, and they should be monitored carefully as they could give rise to more serious hypersensitivity type reactions. Key updates also include warnings that adhering to the daily dose is critical for establishing the proper maintenance dose of Alhemo and that missed consecutive doses of Alhemo will severely limit the efficacy of this product. There was also the option for prescribers to consider under certain circumstances to monitor plasma concizumab concentrations throughout chronic use of this therapy in consultation with the patient.

The overall benefit-risk profile of Alhemo is considered favourable when the product is used in accordance with instructions provided in the product monograph.

A notice of compliance was recommended.

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