Regulatory Decision Summary for Alhemo

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

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Type of Submission:

New Drug Submission (New Active Substance)

Decision issued:

Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations

What was the purpose of this submission?

The purpose of this New Drug Submission (NDS), filed by Novo Nordisk Canada Inc., was to seek marketing authorization under the Priority Review Pathway for Alhemo for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages 12 years and older with hemophilia B (congenital factor IX deficiency) with factor IX inhibitors. The submission was reviewed using the international review work sharing model with the Access Consortium. Health Canada reviewed the Quality and Clinical modules, the Australian Therapeutic Goods Administration (TGA) independently reviewed the Clinical module and Swissmedic reviewed the Non-clinical module. The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

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 B (congenital factor IX [FIX] deficiency) who have FIX 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 B (FIX activity >2%).

Why was the decision issued?

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 B patients with FIX 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 (spontaneous and traumatic) compared to patients treated with on-demand bypassing agents. This was reported as a mean annualized bleed rate (ABR) 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 therapy in a rare patient population who have limited treatment options.

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 and they should be monitored carefully as they could give rise to more serious hypersensitivity type reactions.

The overall benefit-risk profile of Alhemo is considered favourable when the product is used in accordance with instructions provided in the product monograph. For further details about Alhemo, please refer to the product monograph approved by Health Canada and available through the Drug Product Database.

Date of Decision:


Manufacturer / Sponsor:

Novo Nordisk Canada Inc.

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Prescription status:

Available by prescription only

Date Filed: