Hemophilia Drug Effective in Phase 3 Trial


Emicizumab prophylaxis decreases bleeding episodes in hemophilia A patients.

The hemophilia A drug, emicizumab prophylaxis, met the primary endpoint in a phase 3 study, demonstrating a statistically significant reduction in the amount of bleeds over time, according to a Genentech company press release.

Emicizumab is an investigational bi-specific, monoclonal antibody designed to bring together factors IXa and X. These are proteins that are required to activate the natural coagulation cascade and restore the blood clotting process.

HAVEN 1 is the first randomized, multi-center, open-label, phase 3 study evaluating the safety, efficacy, and pharmacokinetics of emicizumab prophylaxis versus no prophylaxis, in patients with hemophilia A and inhibitors to factor VIII.

The investigators enrolled 190 patients with hemophilia A with inhibitors to factor VIII, who were previously treated with episodic or prophylactic bypassing agents, according to the release. The participants were age 12 or older.

Patients previously treated with an episodic bypassing agent were randomized 2:1 to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B). In Arm C, patients previously treated prophylactically with bypassing agents were given emicizumab prophylaxis.

Episodic treatment of breakthrough bleeds with bypassing agents was allowed per protocol, according to the company report.

The study’s primary endpoint was the number of bleeds over time with emicizumab prophylaxis (Arm A) versus no prophylaxis (Arm B). The secondary endpoints included all bleed rate, spontaneous bleed rate, joint bleed rate, target joint bleed rate, health-related quality of life (HRQoL)/health status, in an intra-patient comparison to bleed rate with people who received a prior prophylaxis regimen with bypassing agents (Arm C) and safety.

The most common adverse events for emicizumab were injection site reactions, which were consistent with prior studies.

“The development of inhibitors that render factor VIII replacement less effective, or ineffective, is one of the greatest challenges in the treatment of hemophilia A today, putting patients at high risk for life-threatening bleeds and repeated bleeds that may cause long-term joint damage,” said Sandra Horning, MD, Genentech chief medical officer and head of Global Product Development. “We are pleased to see that, in our first pivotal trial, emicizumab prophylaxis significantly reduced the number of bleeds over time in people in this difficult-to-treat setting. We look forward to working with health authorities to bring this treatment to the hemophilia community as soon as possible.”

As previously reported, 2 patients experienced thromboembolic events, and 2 patients developed thrombotic microangiopathy, which occurred in patients who were on emicizumab prophylaxis, as well as an activated prothrombin complex concentrate to treat break through bleeds, according to the release. Anti-coagulation therapy was not required for both thromboembolic events, and 1 patient restarted emicizumab. Both TMA cases were completely resolved, and 1 patient restarted emicizumab.

“Since the mid-1990’s, there have been incremental improvements in the treatment of hemophilia A with inhibitors,” said Alain Baumann, chief executive officer of the World Federation of Hemophilia. “The current burden of treatment is significant. WFH is supportive of research that could yield new therapeutic agents and offer a new treatment option for inhibitor patients. Filling this need would be a significant advance in our quest to achieve Treatment for All including those living with inhibitors.”

Emicizumab can be administered by a once-weekly injection of a ready-to-use solution subcutaneously, and future trials of the drug will examine less frequent dosing schedules.

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