Chugai Pharmaceutical has announced that the primary endpoint has been met for the global phase III HAVEN 3 (NCT02847637) study evaluating emicizumab (ACE910) subcutaneous injection, once a week and once every two weeks, in patients with haemophilia A (12 years of age or older) without inhibitors to factor VIII. A statistically significant reduction in the number of bleeds was confirmed in patients treated with emicizumab prophylaxis compared to those receiving no prophylactic treatment.
The study also met a secondary endpoint that once-weekly emicizumab prophylaxis was superior to factor VIII prophylaxis, as demonstrated by a statistically significant and clinically meaningful reduction in treated bleeds in an intra-patient comparison of patients receiving emicizumab prophylaxis compared to their prior factor VIII prophylaxis. The most common adverse events with emicizumab were injection site reactions, consistent with prior studies. No thrombotic events occurred in this study. Further details will be presented at a future medical meeting.
“Prophylactic factor VIII replacement therapy is a standard treatment for hemophilia A patients without inhibitors. However, some patients and their caregivers have difficulties with the frequent intravenous injections in their daily life,” said Chugai’s senior vice president, head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. “As a subcutaneous injection, emicizumab can be administered more easily. Today’s results, which are consistent with data reported from patients with inhibitors earlier this year, showed that emicizumab may have the potential to become an efficacious treatment option for hemophilia A patients without inhibitors. We expect emicizumab to provide benefits to a wide range of patients with haemophilia A.”
Emicizumab is an investigational bispecific monoclonal antibody, which was developed using Chugai’s proprietary antibody engineering technologies. The drug is designed to bind factor IXa and factor X. In doing so, emicizumab provides the cofactor function of factor VIII in people with haemophilia A, who either lack or have impaired coagulation function of factor VIII1,2). In November this year, the drug (US product name: HEMLIBRA®; Genentech) was approved by the US Food and Drug Administration “for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and paediatric patients with haemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors”. An EU marketing authorization application was submitted in June 2017 and is being reviewed under Accelerated Assessment by the European Medicines Agency. In Japan, emicizumab obtained an orphan drug designation in August 2016 from the Ministry of Health, Labour and Welfare for the prevention and reduction of bleeding episodes in patients with congenital FVIII deficiency (haemophilia A) who developed inhibitors to FVIII, followed by an application for regulatory approval filed in July 2017.
HAVEN 3 study is a randomized, multicentre, open-label phase III study evaluating the efficacy, safety and pharmacokinetics of emicizumab prophylaxis subcutaneous injection once a week and once every two weeks. The study enrolled 152 patients with hemophilia A, 12 years of age or older without inhibitors to factor VIII, who were previously treated with episodic or prophylactic factor VIII therapy. The primary endpoint of the study is the number of bleeds over time with emicizumab prophylaxis (Arm A and Arm B) versus no prophylaxis (Arm C). Secondary endpoints include joint bleed rate, target joint bleed rate, health-related quality of life (HRQoL)/ health status, intra-patient comparison to bleed rate on their prior prophylaxis regimen with factor VIII therapy (Arm D) and safety.