Hemophilia Drug Emicizumab Succeeds in Phase 3 Study

Prophylactic treatment meets all primary and secondary endpoints

The primary endpoint has been met in a pivotal phase 3 study evaluating prophylactic treatment with emicizumab (Chugai Pharmaceutical Co./Roche/Genentech) in patients 12 years of age or older with hemophilia A and inhibitors to factor VIII. The study showed a statistically significant reduction in the number of bleeds over time in patients treated with emicizumab prophylaxis compared with those receiving no prophylactic treatment.

The study also met all secondary endpoints, including a statistically significant reduction in the number of bleeds over time with emicizumab prophylaxis treatment in patients who had received prior bypassing-agent prophylaxis treatment.

Emicizumab is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X—proteins required to activate the natural coagulation cascade and restore the blood-clotting process. Emicizumab is administered via a subcutaneous injection of a ready-to-use solution once weekly.

HAVEN 1 was a randomized, open-label study evaluating the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis compared with no prophylaxis in patients with hemophilia A and inhibitors to factor VIII. The study included 109 patients (12 years of age or older) with hemophilia A and inhibitors to factor VIII who were previously treated with episodic or prophylactic bypassing agents. Patients previously treated with episodic bypassing agents were randomly assigned to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B). Patients previously treated prophylactically with bypassing agents received emicizumab prophylaxis (Arm C). Episodic treatment of breakthrough bleeds with bypassing agents was allowed.

The study’s primary endpoint was the number of bleeds over time with emicizumab prophylaxis compared with no prophylaxis. Secondary endpoints included the all bleed rate; the joint bleed rate; the spontaneous bleed rate; the target joint bleed rate; the patient’s health-related quality of life/health status; an intrapatient comparison with the bleed rate on their prior prophylaxis regimen with bypassing agents (Arm C); and safety.

The most common adverse events with emicizumab were injection-site reactions. Two patients experienced thromboembolic events, and two patients developed thrombotic microangiopathy (TMA). The common aspect among all cases of thromboembolic events and TMA is that they occurred in patients who were receiving emicizumab prophylaxis and also received activated prothrombin complex concentrate to treat breakthrough bleeds. Neither thromboembolic event required anticoagulation therapy, and one patient restarted emicizumab. Both cases of TMA have completely resolved, and one patient restarted emicizumab.

Hemophilia A affects approximately 320,000 people worldwide, and about 50% to 60% of those individuals have a severe form of the disorder. People with hemophilia A lack or do not have enough of a clotting protein, factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult if not impossible to obtain a level of factor VIII that is sufficient to control bleeding.

Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.

Source: Roche; December 22, 2016.