Hemlibra (Emicizumab-KXWH) for Hemophilia

Last updated Sept. 20, 2022, by Teresa Carvalho, MS

Fact-checked by Joana Carvalho, PhD


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 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. in 2018 to hemophilia A patients without FVIII inhibitors.

The therapy has also been approved in Japan for the treatment of acquired hemophilia A.

In more than 100 countries worldwide, Hemlibra 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, contained in a vial with a sky blue cover
  • 60 mg/0.4 mL, contained in a vial with a purple cover
  • 105 mg/0.7 mL, contained in a vial with a turquoise blue cover
  • 150 mg/mL, contained in a vial with a brown cover

The recommended loading dose is 3 mg/kg once every week for the first month, followed by a maintenance dose of:

  • 1.5 mg/kg once every week, or
  • 3 mg/kg once every two weeks, or
  • 6 mg/kg once every four weeks

The therapy should only be used under the supervision of a healthcare professional. Injection may be performed by patients themselves or given by caregivers, but always after proper training. Self-injection is not recommended for children younger than 7.

Patients should rotate the injection site. Parts of the body that can receive the injection include the upper outer arms (only given by a caregiver or healthcare provider), thighs, and abdomen.  Skin areas that are irritated, reddened, bruised, infected, or scarred should be avoided.

The medication should be stored in the fridge, and should not be frozen or shaken. To protect the medication from light, vials should be kept inside their original carton until use. Unopened bottles can be stored at room temperature, but no longer than seven days or at a temperature greater than 86 degrees Fahrenheit (30 degrees Celsius). Vials should be taken out of the fridge 15 minutes before injection to allow the medication to reach room temperature prior to administration.

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 113 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 bypassing 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).

HAVEN 3 trial

Launched in 2016, HAVEN 3 (NCT02847637) evaluated 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.

Ongoing trials

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

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

Other, less common side effects should also be taken into consideration, namely blood clots and blood vessel damage.

Blood clots

Thrombotic, or blood clotting, events have been reported in patients on Hemlibra who were also given an activated prothrombin complex concentrate (aPPC; sold as FEIBA) to control bleeds. Hemlibra can also interfere with certain blood clotting tests. Treatment should be discontinued if blood clotting signs occur. Restarting the treatment after symptom resolution should only be considered after assessing the benefits and risks on a patient-by-patient basis.

Blood vessel damage

The FDA label has a boxed warning alerting healthcare professionals and patients that Hemlibra may cause thromboembolism (blood vessel obstruction due to blood clots) and thrombotic microangiopathy (TMA) — a condition in which blood clots cause damage to the body’s small blood vessels — when used together with FEIBA, particularly at a cumulative dose greater than 100 units/kg/day for more than one day. As with blood clots, in the presence of TMA signs, treatment should be discontinued. Once these signs resolve, patients may resume treatment after considering the benefits and risks.

Development of antibodies

Development of antibodies against Hemlibra may occur during treatment. In some cases, this is related to a reduction in the treatment’s efficacy. The therapy’s label recommends monitoring for signs of efficacy loss. If antibodies are suspected, other treatments should be considered.

Use in pregnancy and breastfeeding

It is unknown if Hemlibra can affect the developing fetus or pass to breast milk. Patients who plan to become pregnant or breastfeed should talk with their healthcare team and only continue treatment during these periods if the potential benefit justifies the potential risks to the fetus or infant.

 


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