Emicizumab Meets Endpoints for Hemophilia A in HAVEN Trials

New findings from Genentech indicate that emicizumab prophylaxis reduces the number of bleeds in children under 12 years old with hemophilia A and inhibitors to factor VIII.

Released April 16, interim results from the phase 3 HAVEN study are consistent with initial findings, showing that emicizumab, a drug designed to bring together the proteins required to restore the blood clotting process, was effective in reducing the number of bleeds in adolescents and adults with hemophilia A and inhibitors to factor VIII.

New interim results were collected after a median of 12 weeks of treatment, and demonstrated a statistically significant and clinically meaningful reduction in the number of bleeds over time compared to no prophylaxis, as well as compared to prior prophylaxis with bypassing agents. The most common adverse events were injection site reactions and common cold symptoms.

“Managing hemophilia A with inhibitors to factor VIII is especially challenging for children and their caregivers, because bleeding is difficult to control and current treatments require frequent intravenous infusions,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech. “We are … pleased to share these results with the community as we join in celebrating World Hemophilia Day [April 17].”

HAVEN 2 is the second phase 3 study in the emicizumab clinical development program. It is a single-arm, multicenter, open-label phase 3 study evaluating the efficacy, safety and pharmacokinetics of once-weekly subcutaneous administration of emicizumab. The interim analysis after a median of 12 weeks of treatment included 19 children less than 12 years of age with hemophilia A and inhibitors to factor VIII, who require treatment with bypassing agents.

The study aims to evaluate emicizumab prophylaxis based on the number of bleeds over time, safety, pharmacokinetics, health-related quality of life (HRQoL) and proxy HRQoL with aspects of caregiver burden. The study will enroll a total of 60 children for its final analysis planned after 52 weeks of treatment with emicizumab.

Two additional phase 3 studies of emicizumab are ongoing:

• HAVEN 3, evaluating emicizumab prophylaxis dosed once weekly or once every other week in people 12 years of age or older with hemophilia A without inhibitors to factor VIII
• HAVEN 4, evaluating emicizumab prophylaxis dosed every four weeks in people 12 years of age or older with hemophilia A with or without inhibitors to factor VIII

The initial HAVEN 1 study was a phase 3 study evaluating the efficacy, safety and pharmacokinetics of emicizumab prophylaxis versus no prophylaxis in people with hemophilia A and inhibitors to factor VIII. HAVEN 1 included 109 patients 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 randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B). Patients previously treated prophylactically with bypassing agents received emicizumab prophylaxis (Arm C).

Data from both HAVEN 1 and the interim data from HAVEN 2 studies will be presented at an upcoming medical meeting before emicizumab is submitted to health authorities for approval. The drug, if eventually approved, has the potential to be a blockbuster for the company.

Results from the trials were announced this week in a press release from Genentech.