Hemlibra (emicizumab-KXWH) is an approved treatment to manage the symptoms of hemophilia type A in people with factor VIII inhibitors.

Administered as a once-weekly under-the-skin injection, it was originally developed by Japan’s Chugai Pharmaceuticals, which is now part of the Roche group. Further development of this therapy is underway in collaboration with Genentech, a Roche subsidiary.

How Hemlibra works

Hemophilia A is an inherited disorder, caused by a mutation in the coagulation factor VIII gene. Factor VIII is an essential protein for the blood to clot properly. Normally, this protein binds to both factors IX and X, activating factor X and initiating blood clotting. A deficiency in the factor VIII protein can cause excessive internal and external bleeding.

Hemlibra is a bispecific antibody, a protein designed to bind to two specific targets. It mimics the action of factor VIII by binding to both factor IX and factor X in place of the missing factor VIII. This helps blood to clot normally, reducing blood loss and preventing damage to joints and tissues from internal bleeding.

Current hemophilia A treatments generally involve infusions of a recombinant factor VIII protein. However, around 30 percent of patients develop inhibitors against recombinant factor VIII, rendering such treatments ineffective. Hemlibra is effective in patients with hemophilia A with inhibitors, and it can be more effective and remain active in the body for longer than other bypassing agents (BPAs).

Hemlibra in clinical trials

On August. 24, 2017, the U.S. Food and Drug Administration (FDA) accepted the biologics license application (BLA) for Hemlibra in patients with inhibitors and granted Hemlibra priority review status in August 2017. In November, Hemlibra was approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeds in adults and children with hemophilia type A with inhibitors, making it the first new medicine in nearly 20 years to treat these patients.

Roche has also submitted a marketing authorization application to the European Medicines Agency (EMA). The application was based on results of the Phase 3 HAVEN 1 trial (NCT02622321), and interim data from the Phase 3 HAVEN 2 trial (NCT02795767).

Results of HAVEN 1 appeared in the New England Journal of Medicine. The Phase 3, open-label, multicenter and randomized trial assessed the safety and efficacy of Hemlibra prophylaxis in 109 patients, ages 12 or older, with hemophilia A with inhibitors against factor VIII. The study had three main groups: patients who had previously received on-demand BPAs were assigned Hemlibra prophylaxis (group A) or no prophylaxis (group B), and patients who had previously been on BPA prophylaxis were given Hemlibra prophylaxis (group C). A fourth group (group D) consisted patients who enrolled after groups A, B and C had closed. All patients could take on-demand BPAs, if needed.

Patients receiving Hemlibra prophylaxis had a significant reduction (87 percent) in the treated annualized bleed rate compared to those only given on-demand BPAs (group A compared to B). Patients in group C saw a significant improvement (79 percent) in the annualized bleed rate on Hemlibra prophylaxis compared to previous BPA prophylaxis.

Hemlibra’s safety profile was acceptable, with the most common side effects being injection-site reactions, headache, fatigue, upper respiratory tract infections, and joint pain.

Interim results for the single-arm, multicenter, open-label, HAVEN 2 trial (NCT02795767) were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Meeting, on July 10, 2017. Data was reported on 19 patients and showed that, at a median of 12 weeks of once-weekly Hemlibra prophylaxis, 94.7 percent had zero treated bleeds, and 63.2 percent had zero overall bleeds. After a median observation time of 38.1 weeks, 87 percent of patients who received Hemlibra prophylaxis had zero treated bleeds, and 34.8 percent had zero overall bleeds.

Another Phase 3 trial, called HAVEN 3, (NCT02847637) evaluated Hemlibra prophylaxis in adult hemophilia A patients without factor VIII inhibitors. Results of this trial were announced in November 2017 and showed a significant reduction in the number of bleeds in treated patients treated compared to those who did not receive prophylaxis. The study also showed that once-weekly Hemlibra prophylaxis was better than factor VIII prophylaxis since it significantly reduced the number of treated bleeds compared to factor VIII. The most common side effects of Hemlibra use were injection-site reactions. No thrombotic events were observed.

A further Phase 3 clinical trial, called HAVEN 4, (NCT03020160) is assessing the efficacy and safety of Hemlibra prophylaxis given at a reduced rate — 6 mg/kg every four weeks — in adult hemophilia A patients with or without factor VIII inhibitors. The trial is ongoing in the U.S., Australia, Europe, and Japan but no longer recruiting participants; it is expected to conclude in July 2018.

***

Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.