Regulatory Decision Summary for Hemlibra

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.

Product type:


Medicinal ingredient(s):

emicizumab injection

Therapeutic area:


Type of submission:

New Drug Submission

Control number:

What was the purpose of this submission?


Hoffmann-La Roche Limited filed a New Drug Submission for Hemlibra (emicizumab injection), indicated for hemophilia A (congenital factor VIII deficiency) patients with factor VIII inhibitors as routine prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes.


Why was the decision issued?


Hemlibra (emicizumab injection) is an engineered humanized monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific antibody structure bridging factor IXa and factor X. It replaces the natural function of activated factor VIII (FVIII), which is missing in hemophilia A patients and is needed for effective hemostasis.

Authorization of Hemlibra was based on results from a pivotal Phase III study (Haven 1) of hemophilia A patients who were ≥ 12 years of age and from a single-arm supportive study (Haven 2) of pediatric hemophilia A patients who were from 1 to ≤ 12 years of age. The patients enrolled in these studies no longer responded to exogenous FVIII treatment because they had developed antibodies against FVIII (FVIII inhibitors) that makes this mainstay therapy ineffective. In the pivotal study, 51 male patients with FVIII inhibitors, the majority who had severe hemophilia A (94%), were randomized 2:1 to receive either Hemlibra (n = 34) or no prophylaxis (n = 17). In the supportive study, 23 pediatric male patients with FVIII inhibitors received at least 12 weeks of Hemlibra prophylaxis and 13 patients were part of a non-interventional study that monitored bleeds prior to study entry.

The primary efficacy endpoint was the number of bleeds requiring treatment with coagulation factors over time, calculated as an annualized bleed rate (ABR). In the pivotal study, patients randomized to Hemlibra experienced a median ABR of 2.9 that was considerably lower than the median ABR of 23.3 for patients who did not receive Hemlibra. In the supportive study, 23 pediatric patients who received at the least 12 weeks of Hemlibra therapy had an ABR rate of 0.2. For the 13 pediatric patients who were part of a non-interventional study, the ABR for treated bleeds was significantly reduced with Hemlibra prophylaxis, from an ABR of 17.2 in the non-interventional study to an ABR of 0.2 following once weekly Hemlibra treatment. Overall, the clinical studies demonstrated that Hemlibra prophylaxis reduced the number of bleeds requiring treatment in pediatric, adolescent and adult hemophilia A patients with FVIII inhibitors.

Serious thromboembolic and thrombotic microangiopathy events have occurred in some hemophilia A patients on Hemlibra prophylaxis who also received activated prothrombin complex concentrate (aPCC). This risk has been addressed by additional information in the Product Monograph.

The recommended dose of Hemlibra is 3 mg/kg once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, administered as a subcutaneous injection.

Health Canada granted this application priority review. A Notice of Compliance (NOC) was recommended based on a positive benefit-risk profile of Hemlibra prophylaxis in hemophilia A patients with FVIII inhibitors.

For more information on Health Canadas decision, please view the Summary Basis of Decision.


Decision issued

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