Rare Disease Report

Prophylaxis Therapy for Hemophilia A Patients With Factor VIII Inhibitors Under Review by the FDA

AUGUST 24, 2017
James Radke
The U.S. Food and Drug Administration (FDA) has accepted Genentech’s Biologics License Application (BLA) and granted Priority Review for emicizumab to prophylactically treat patients with hemophilia A with factor VIII inhibitors.

Hemophilia A is a genetic bleeding disorder that affects approximately 20,000 people in the United States. The disorder is due to patients not having enough factor VIII that combines factors IXa and X in the clotting cascade. Most treatments for hemophilia A involve factor replacement therapy, but about one-third of with hemophilia A patients develop inhibitors to standard factor VIII replacement therapies that can limit treatment options.

Emicizumab is a monoclonal antibody that brings together factors IXa and X so it could potentially be effective on both patients who develop factor VIII inhibitors and those who do not.

Because the BLA was given a Priority Review, the FDA is expected to make a decision within 6 months (by February 23, 2018).

THE BLA includes data from numerous clinical trials, including a Phase 3 study (HAVEN-1) recently published in The New England Journal of Medicine involving teens and adults with hemophilia A, and interim Phase 3 results in children (HAVEN-2) that was presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress in July 2017.

In the HAVEN-1 study published in the New England Journal of Medicine, hemophilia A patients with inhibitors that took emicizumab prophylaxis had significantly fewer bleeding events and improved health-related quality of life scores compared to controls.

More specifically, patients (n=109) received once-weekly subcutaneous emicizumab (3 mg/kg for 4 weeks followed by 1.5 mg/kg weekly) or no prophylactic treatment. The median age was 28 years. All but 7 patients had a severe form of hemophilia A.
Results of the study revealed that patients taking once-weekly emicizumab prophylaxis had annualized bleeding rate of 2.9 events compared to 23.3 events in patients not receiving prophylactic treatment. Further, 63% of participants in the emicizumab group experienced 0 bleeding events throughout the 24-week trial. Only 6% of patients in the control group experienced 0 bleeding events.
Throughout the study, 198 adverse events (AE) were reported in 103 participants receiving emicizumab prophylaxis, the most frequently-reported of which were injection-site reactions, which occurred 15% (28 occurrences in 15 patients) of the time. The only AE that was severe in intensity was a moderate event of injection-site hematoma, which occurred on trial day 2 and resolved on trial day 28.
In the HAVEN-2 study involving children (12 years or younger) with hemophilia A who had inhibitors to factor VIII, interim results showed the drug is also safe and effective in children.

After a median time of 12 weeks of treatment, only 1 of the 19 children in the study has reported a bleed that required treatment. The most common AEs were mild injection site reactions and common cold symptoms (nasopharyngitis).

In a news release, Sandra Horning, M.D., chief medical officer and head of Global Product Development at Genentech said, “Results of our Phase III study in adults and adolescents as well as early Phase III results in children showed that emicizumab has significant potential to help people with hemophilia A with inhibitors, who face major challenges in preventing and treating bleeds. We are working with the FDA to hopefully bring this new prophylactic treatment option to the hemophilia A inhibitor community as soon as possible.”

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