by Eric Lowe

On November 11th 2017, Genentech announced that the study drug, widely known as ACE910 (emicizumab), had been FDA-approved for prophylaxis treatment

in children and adults with hemophilia A and inhibitors to prevent or lessen bleeding episodes. This approval snapped a streak of nearly 20 years for the inhibitor population on newly-approved treatment products.

Almost 1 in 3 hemophilia A patients that are treated with factor VIII replacement therapy tend to develop inhibitors against factor VIII, which can lead to a higher risk for bleeds and long-term joint damage. The FDA-approved drug, now named Hemlibra, bypasses that problem as it is a bispecific factor IXa- and factor X-directed antibody. This means its use can bring together the two proteins, which will activate the natural clotting cascade. Hemlibra also requires only once a week use as an injection under the skin.1

Hemlibra, has had positive results from two studies, HAVEN 1 (NCT02622321) for patients 12 years of age or older with hemophilia A with inhibitors, and HAVEN 2 (NCT02795767) for patients younger than 12 years with hemophilia A with inhibitors. Results indicated that Hemlibra significantly reduced bleeds in both adult and pediatric patients with hemophilia A.

“People with hemophilia A who develop inhibitors face significant challenges preventing and controlling bleeds and typically require infusions of medicine multiple times a week, which can be especially difficult for young children and their families,” Dr. Guy Young, professor of pediatrics at University of Southern California Keck School of Medicine, said in a press release. “This new medicine has been shown to reduce the frequency of bleeds compared to the currently available medicines and only needs to be injected once a week. This could make a meaningful difference for these children.”1

Results

Phase 3 of the HAVEN 1 study (in patients 12 or older) showed an 87% bleed-reduction when using Hemlibra compared to those who did not treat prophylactically, and a 79% bleed-reduction was reported for those who did treat prophylactically with a different bypassing agent (BPA) before switching to Hemlibra.

Similarly, the HAVEN 2 study (in patients younger than 12) also showed an 87% bleed-reduction when beginning prophylactic treatment with Hemlibra, and a 99% bleed- reduction when changing their prophylactic treatments from a BPA to Hemlibra. Common side effects of treatment were injection site reactions, headache, and joint pain (arthralgia).1

One death has occurred in the HAVEN 1 study back in February 2017. The patient received bypassing agents (BPA) after experiencing a serious rectal hemorrhage.2 The patient’s repeated use of the BPA in combination with the remaining residual amounts of Hemlibra in the patient’s system caused threat of serious thrombotic events. After discontinuation of the (BPA), the patient showed improvement. But Roche said the hemorrhage therapy was complicated because the patient declined blood transfusions. The trial investigator determined that the cause of death was the rectal hemorrhage, not emicizumab.2 You may read more details on this using the #2 resources link below.

Looking Ahead

Hemlibra’s availability in the US is currently emerging and evolving.

HAVEN 3 and HAVEN 4 studies are currently underway to evaluate the treatment’s efficacy and safety at other doses and schedules. HAVEN 3 (NCT02847637) is being conducted in patients 12 and older for those with hemophilia A without inhibitors with doses given once every 1-2 weeks.

HAVEN 4 (NCT03020160) is being conducted in patients 12 years or older, with or without inhibitors, with doses given every four weeks after an initial one-month “loading” period.

1. https://hemophilianewstoday. com/2017/11/17/fda-approves-hemlibra- by-genentech-to-treat-hemophilia-a- patients-with-factor-viii-inhibitors/?utm_ source=Hemophilia+News&utm_ campaign=58c1c52d86-RSS_EMAIL_ CAMPAIGN&utm_medium=email&utm_ term=0_ab10fdd11a-58c1c52d86-72167405

2. https://hemophilianewstoday.com/2017/02/24/ death-of-hemophiliac-in-clinical-trail-raises- more-concern-about-emicizumab/