Hemophilia therapy Hemlibra® (emicizumab-kxwh) is a humanized, monoclonal, modified immunoglobulin G4, bispecific antibody binding factor IXa and factor X, and it is produced from genetically modified Chinese hamster ovary cells. Use of Hemlibra is not associated with the development of inhibitors to factor VIII (FVIII) due to its distinct molecular structure. It is formulated as a sterile, colorless to slightly yellow solution supplied in single-dose vials containing either 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, or 150 mg/mL. The route of administration is subcutaneous (SC).1

Indications 

Hemlibra is US Food and Drug Administration (FDA)-approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients, including newborns, with hemophilia (HEM) A with or without  FVIII inhibitors.1

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Efficacy

HAVEN 3 and HAVEN 4 are two clinical trials that evaluated the efficacy of Hemlibra for routine prophylaxis in adult and adolescent patients with HEM A without inhibitors. In the randomized, multicenter, open-label trial, HAVEN 3, patients treated with either 1.5 mg/kg or 3 mg/kg of Hemlibra had a 96% and 97% reduction in annualized bleeding rate (ABR), respectively, among treated bleeds compared to participants who did not receive any prophylaxis (P <.0001). There were also statistically significant (P <.0001) reductions in the ABRs for total bleeds (95% reduction for 1.5 mg/kg; 94% reduction for 3 mg/kg), treated spontaneous bleeds (94% reduction for 1.5 mg/kg, 98% reduction for 3 mg/kg), treated joint bleeds (96% reduction for 1.5 mg/kg, 97% reduction for 3 mg/kg), and treated target joint bleeds (95% reduction for both 1.5 mg/kg and 3 mg/kg) compared to those in participants receiving no prophylaxis.2 The HAVEN 4 study, which enrolled patients with and without FVIII inhibitors, reported that the ABR for treated bleeds in patients receiving prophylactic Hemlibra at a dose of 6 mg/kg was 2.6, and 27.8% experienced no bleeds during the observation period (range 24.1-29.4 weeks).3 HAVEN 4 was a single-arm study, however, for comparison, the ABR for treated bleeds in patients receiving no prophylaxis in HAVEN 3 was 38.2.1

HAVEN 1 was a randomized, multicenter, open-label clinical trial evaluating the efficacy of Hemlibra in patients over 12 years of age with HEM A and FVIII inhibitors who previously received either on-demand or prophylactic treatment with bypassing agents. Patients who received prophylaxis with 1.5 mg/kg Hemlibra had an 87% reduction in ABR for treated bleeds (P <.0001) and an 80% reduction in ABR for all bleeding events (P <.0001) compared to patients not receiving prophylaxis. Compared to patients on previous bypassing agent prophylaxis, patients receiving Hemlibra experienced a 79% reduction in ABR for treated bleeds (3.3 vs 15.7; P =.003).1,4 

In HAVEN 2, a single-arm, multicenter, open-label clinical trial, the safety of Hemlibra as prophylaxis was evaluated in pediatric patients aged <12 years with HEM A and FVIII inhibitors. The ABR for treated bleeds was 0.3, and the ABR for all bleeds was 3.8.  Of the enrolled patients, 55.9% experienced no bleeds during the observation period (range 18.4-63 weeks).1,5

Dose

The recommended loading dose is 3 mg/kg SC once weekly for 4 weeks. The maintenance dose can be a SC injection of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks.1 

Adverse Events and Safety Information

Common adverse events include headache, joint pain, and erythema, pain, warmth, tenderness, or itching at the injection site.1

Serious adverse events include thrombotic microangiopathy (TMA) and other thrombotic events. Symptoms of TMA include confusion, weakness, limb edema, jaundice, abdominal pain, back pain, nausea, vomiting, and oliguria. Potential signs and symptoms of thrombotic events include limb edema, limb erythema, dyspnea, chest pain or tightness, tachycardia, hematemesis, lightheadedness, headache, facial numbness, eye pain or swelling, and vision loss.1

There are no available data on the use of Hemlibra in pregnant women, and it is unknown whether there is potential for fetal harm. It should only be used in this population if the benefits outweigh the risks.1

References

1. Hemlibra. Prescribing Information. Genentech, Inc.; 2018. Accessed January 3, 2022.

2. Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822. doi:10.1056/NEJMoa1803550

3. Pipe SW, Shima M, Lehle M, et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019;6(6):e295-e305. doi:10.1016/S2352-3026(19)30054-7

4. A study to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in hemophilia A participants with inhibitors (HAVEN 1). ClinicalTrials.gov. December 4, 2015. Updated June 24, 2021. Accessed January 3, 2022.

5.  A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors (HAVEN 2).ClinicalTrials.gov. June 10, 2016. Updated June 2, 2021. Accessed January 3, 2022.

Reviewed by Harshi Dhingra, MD, on 1/3/2022.