Hemlibra (Emicizumab-KXWH)

What is Hemlibra for Hemophilia?

Hemlibra (emicizumab-KXWH) is an antibody-based therapy used to prevent or reduce bleeds in people with hemophilia A, both with and without factor VIII (FVIII) inhibitors.

It was originally developed by Chugai Pharmaceutical, which is now part of the Roche group. Further development and marketing are being conducted in collaboration with Genentech, a Roche subsidiary.

How does Hemlibra work?

Hemophilia A is an inherited bleeding disorder, caused by a mutation in the gene encoding FVIII, an essential blood-clotting protein. Normally, this protein binds to both factor IX (FIX) and factor X (FX) to initiate blood clotting. A deficiency in FVIII can cause excessive and prolonged bleeding.

Hemlibra is a bispecific antibody that is designed to bind to two specific targets, mimicking the action of FVIII, and thereby preventing or lowering the frequency of bleeding episodes in people with hemophilia A. The medication also is effective in patients with FVIII inhibitors — neutralizing antibodies targeting FVIII that might render standard replacement therapies ineffective.

Who can take Hemlibra?

Hemlibra was initially approved by the U.S. Food and Drug Administration (FDA) in 2017 to prevent or reduce the frequency of bleeding episodes in children and adults with hemophilia A with FVIII inhibitors. Its approval was extended in the U.S. the following year, in 2018, to hemophilia A patients without FVIII inhibitors.

In more than 100 countries worldwide, Hemlibra currently is approved for the treatment of hemophilia A patients with FVIII inhibitors.

Who should not take Hemlibra?

According to the therapy’s prescribing information, there are no contraindications for its use.

How is Hemlibra administered?

Hemlibra is given as an under-the-skin or subcutaneous injection and is available in single-dose bottles containing one of the following strengths:

  • 30 mg/mL
  • 60 mg/0.4 mL
  • 105 mg/0.7 mL
  • 150 mg/mL

The recommended loading dose is 3 mg/kg once every week for the first month, then a maintenance dose of 1.5 mg/kg once every week.

Hemlibra in clinical trials

Hemlibra’s original approval came on the heels of positive results from two of the largest clinical studies in hemophilia A patients with FVIII inhibitors, the HAVEN 1 and HAVEN 2 trials.

HAVEN 1 trial

A Phase 3 trial, HAVEN 1 (NCT02622321) involved 109 patients, ages 12 or older. The open-label, multicenter, and randomized trial assessed the safety and efficacy of Hemlibra in preventing bleeds (prophylaxis) in these patients. Those who had previously been treated with bypassing agents were randomly assigned to receive Hemlibra prophylaxis (group A) or no prophylaxis (group B). Patients who had previously received prophylactic treatment with bypassing agents received Hemlibra prophylaxis in group C.

Patients receiving prophylactic treatment with Hemlibra saw their annual bleeding rate drop by 87% compared with those not receiving the preventive medicines. Patients in group C also saw their annual bleeding rate drop by 79% while on Hemlibra compared with their previous prophylactic regimen with bypassig agents.

HAVEN 2 trial

HAVEN 2 (NCT02795767) also was a multicenter, open-label Phase 3 trial. The study enrolled 88 patients younger than age 12. Results showed that 77% of children who received Hemlibra prophylaxis had zero treated bleeds. Also, all joint bleeding episodes resolved during the study period. In an intra-patient analysis of 15 children, Hemlibra prophylaxis resulted in a 99% reduction in treated bleeds compared with previous treatment with a bypassing agent (given either as prophylaxis or on-demand).

Ongoing trials

The development and testing of Hemlibra also include the HAVEN 3, 4, 5, and 6 studies. All are Phase 3 trials that are still ongoing. Data from HAVEN 3 and 4 supported Hemlibra’s approval extension to hemophilia A patients without FVIII inhibitors in the U.S.

HAVEN 3 trial

Launched in 2016, HAVEN 3 (NCT02847637) is evaluating Hemlibra prophylaxis in 152 hemophilia A patients, ages 12 or older, without FVIII inhibitors. Results of this trial showed a significant reduction in the number of bleeds in Hemlibra-treated patients compared with those who did not receive prophylaxis. The study also showed that Hemlibra prophylaxis was better than FVIII prophylaxis at reducing bleeding rates.

HAVEN 4 trial

The HAVEN 4 (NCT03020160) study is assessing the efficacy and safety of Hemlibra prophylaxis given at a reduced rate — 6 mg/kg every four weeks — in 48 male adults and adolescents with hemophilia A with or without inhibitors. Data supported a once-monthly dosing schedule. More than half of the patients had no bleeds, and 90.2% had fewer than three bleeds, the results showed.

HAVEN 5 and 6 trials

Involving patients in Asia — specifically China, Hong Kong, Malaysia, and Thailand — HAVEN 5 (NCT03315455) has already confirmed the efficacy of Hemlibra prophylaxis at two doses (1.5 mg/kg once weekly, and 6 mg/kg every four weeks).

HAVEN 6 (NCT04158648) has recently shown the safety and efficacy of Hemlibra in preventing bleeds in people with mild or moderate hemophilia A.

Common side effects of Hemlibra

The most common side effects associated with Hemlibra are:

  • injection site reactions
  • headache
  • arthralgia, or joint pain

The FDA label has a boxed warning alerting healthcare professionals and patients that Hemlibra may cause thrombosis, or blood clots. Hemlibra also can interfere with certain blood-clotting tests.

 

Last updated: March 25, 2022, by Teresa Carvalho, MSc


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