Emicizumab

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Emicizumab
Emicizumab.png
Monoclonal antibody
Type Whole antibody
Source Humanized
Target Activated factor IX, factor X
Clinical data
Trade names Hemlibra
Other namesACE910, RG6013, emicizumab-kxwh
AHFS/Drugs.com Monograph
MedlinePlus a622046
License data
Pregnancy
category
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6434H9940N1724O2047S45
Molar mass 145639.02 g·mol−1

Emicizumab, sold under the brand name Hemlibra, is a humanized bispecific monoclonal antibody for the treatment of haemophilia A, developed by Genentech and Chugai (both organizations are subsidiaries of Hoffmann-La Roche). [4] Emicizumab is a bispecific factor IXa- and factor X-directed antibody. [3] [5] [6]

Contents

Emicizumab was first approved by the U.S. Food and Drug Administration (FDA) in November 2017 for routine prophylaxis in patients with hemophilia A who have developed factor VIII inhibitors. [7] [8] In October 2018, the FDA expanded approval, under the breakthrough therapy designation , to include all patients with hemophilia A, regardless of inhibitor status. [9] [10] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [11]

Medical uses

Emicizumab is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in people with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. [3]

Available forms

Emicizumab is administered as a subcutaneous injection with flexible dosing options. [12] The drug can be administered once weekly, every two weeks, or every four weeks, providing patients and healthcare providers with dosing flexibility based on individual needs and preferences. [12]

The long elimination half-life of approximately 28-32 days supports the extended dosing intervals, making it more convenient compared to traditional factor VIII replacement therapy, which typically requires more frequent administration. [13]

Adverse effects

The most common adverse reactions (incidence ≥10%) are injection site reactions, headache, and arthralgia. [3]

Pharmacology

Pharmacokinetics

The long elimination half-life of approximately 28-32 days supports the extended dosing intervals, making it more convenient compared to traditional factor VIII replacement therapy, which typically requires more frequent administration. [13]

Mechanism of action

Emicizumab is a bispecific antibody that simultaneously binds to activated coagulation factor IX (FIXa) and factor X (FX), bringing these coagulation factors into spatial proximity to facilitate the activation of factor X. [13] This mechanism mimics the natural cofactor function of activated factor VIII (FVIIIa) in the coagulation cascade, effectively replacing the missing or deficient clotting factor in patients with hemophilia A. [14] [4] [15]

Unlike traditional factor VIII replacement therapy, emicizumab functions independently of factor VIII levels and is not neutralized by factor VIII inhibitors. [5] This unique mechanism makes it particularly valuable for patients who have developed inhibitory antibodies against factor VIII, a complication that affects approximately 20-30% of patients with severe hemophilia A. [16]

Research

A Phase I clinical trial found that it was well tolerated by healthy subjects. [17]

Studies indicate that emicizumab is a better therapy compared to the previous generations, due to subcutaneous administration and fewer injections, which reduces injection site reactions and makes therapy less troublesome. [18]

HAVEN clinical trial program

Emicizumab was evaluated in one of the largest pivotal clinical trial programs in hemophilia A, comprising four pivotal Phase III studies known as the HAVEN trials. [19]

HAVEN 1 study

HAVEN 1 was a randomized, multicenter, open-label Phase III trial that included 109 male patients (ages 12-75 years) with severe hemophilia A and factor VIII inhibitors. [20] The study demonstrated that emicizumab prophylaxis significantly reduced bleeding episodes compared to no prophylaxis in patients with inhibitors. [21] [22] [23]

HAVEN 3 study

HAVEN 3 evaluated emicizumab in patients with severe hemophilia A without factor VIII inhibitors. The trial demonstrated that subcutaneous emicizumab prophylaxis, administered either once weekly or every two weeks, resulted in bleeding rates that were significantly lower by more than 95% compared to no prophylaxis. [6] More than 55% of participants in each randomized emicizumab regimen experienced no treated bleeds during the study period. [6] [24]

Additional HAVEN studies

The clinical program also included HAVEN 2 (pediatric patients with inhibitors) and HAVEN 4 (patients switching from bypassing agent prophylaxis), further establishing the efficacy and safety profile of emicizumab across different patient populations. [25]

Regulatory approvals

Emicizumab received its first regulatory approval from the FDA on November 16, 2017, under the brand name Hemlibra for routine prophylaxis in adult and pediatric patients with hemophilia A who have developed factor VIII inhibitors. [7] This approval was based on results from the HAVEN 1 and HAVEN 2 clinical trials. [26] [27]

On October 4, 2018, the FDA expanded the approval under the Breakthrough Therapy designation to include all adult and pediatric patients (newborn and older) with hemophilia A, regardless of inhibitor status. [9] This expanded approval was based on data from the HAVEN 3 and HAVEN 4 studies. [19]

Emicizumab has since received regulatory approvals in numerous countries worldwide, including approval by the European Medicines Agency (EMA) and other international regulatory authorities. [25]

See also

References

  1. 1 2 "AUSTRALIAN PRODUCT INFORMATION – Hemlibra (Emicizumab)". Archived from the original on 15 May 2023. Retrieved 8 January 2023.
  2. ↑ "Summary Basis of Decision (SBD) for Hemlibra". Health Canada . 23 October 2014. Retrieved 29 May 2022.
  3. 1 2 3 4 "Hemlibra- emicizumab injection, solution". DailyMed. 28 October 2024. Retrieved 11 July 2025.
  4. 1 2 Spreitzer H (4 July 2016). "Neue Wirkstoffe - Emicizumab". Österreichische Apothekerzeitung (in German) (14/2016).
  5. 1 2 Syed F, Khurshid H (4 July 2023). "Emicizumab". StatPearls. StatPearls Publishing. PMID   32644408.
  6. 1 2 3 Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. (2018). "Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors". New England Journal of Medicine. 379 (9): 811–822. doi:10.1056/NEJMoa1803550. PMC   5866543 . PMID   29365805.
  7. 1 2 "FDA approves emicizumab-kxwh for prevention and reduction of bleeding in patients with hemophilia A with factor VIII inhibitors". U.S. Food and Drug Administration. 16 November 2017. Retrieved 21 August 2025.
  8. ↑ "Roche hemophilia drug wins FDA nod, with a warning". Reuters. 17 November 2017.
  9. 1 2 "FDA approves emicizumab-kxwh for hemophilia A with or without factor VIII inhibitors". U.S. Food and Drug Administration. 4 October 2018. Retrieved 21 August 2025.
  10. ↑ "FDA Grants Roche Breakthrough Therapy Designation on Hemophilia Drug". BioPharm International. UBM. 19 April 2018. Retrieved 20 April 2018.
  11. ↑ New Drug Therapy Approvals 2017. U.S. Food and Drug Administration (FDA) (Report). January 2018. Archived from the original (PDF) on 14 September 2019. Retrieved 16 September 2020.
  12. 1 2 Yoneyama K, Schmitt C, Portron A, Kiialainen A, Kotani N, Jaminion F, et al. (2023). "Clinical pharmacology of emicizumab for the treatment of hemophilia A". Expert Review of Clinical Pharmacology. 16 (9): 775–790. doi:10.1080/17512433.2023.2243213. PMID   37529848.
  13. 1 2 3 "Emicizumab: Uses, Interactions, Mechanism of Action". DrugBank Online. Retrieved 21 August 2025.
  14. ↑ Malherbe K (January 2019). "Traction apophysitis of the knee: A case report". Radiology Case Reports. 14 (1): 18–21. doi: 10.1016/j.radcr.2018.09.012 . PMC   6187429 . PMID   30305859.
  15. ↑ Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. (May 2016). "Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A". The New England Journal of Medicine. 374 (21): 2044–2053. doi: 10.1056/NEJMoa1511769 . PMID   27223146.
  16. ↑ Gelbenegger G, Schoergenhofer C, Knoebl P, Jilma B (October 2020). "Bridging the Missing Link with Emicizumab: A Bispecific Antibody for Treatment of Hemophilia A". Thrombosis and Haemostasis. 120 (10): 1357–1370. doi:10.1055/s-0040-1714279. PMC   7649063 . PMID   32717759.
  17. ↑ Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, et al. (March 2016). "A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects". Blood. 127 (13): 1633–1641. doi:10.1182/blood-2015-06-650226. PMC   4817308 . PMID   26626991.
  18. ↑ Grabowska K, Grzelak M, Zhao LY, Płuciennik E, Pasieka Z, Kciuk M, et al. (May 2024). "Emicizumab as a Promising Form of Therapy for Type A Hemophilia - A Review of Current Knowledge from Clinical Trials". Current Protein & Peptide Science. 25 (9): 719–737. doi:10.2174/0113892037294674240509094418. PMID   38797909.
  19. 1 2 "FDA Approves Genentech's Hemlibra (emicizumab-kxwh) for People With Hemophilia A Without Factor VIII Inhibitors". Genentech. 4 October 2018. Retrieved 21 August 2025.
  20. ↑ "Emicizumab-kxwh Approved by FDA for Patients With Hemophilia A and Inhibitors". ASH Clinical News. 30 December 2021. Retrieved 21 August 2025.
  21. ↑ Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. (August 2017). "Emicizumab Prophylaxis in Hemophilia A with Inhibitors". The New England Journal of Medicine. 377 (9): 809–818. doi:10.1056/NEJMoa1703068. PMC   5710096 . PMID   28691557.
  22. ↑ Hoffmann-La Roche (26 May 2021). A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients With Inhibitors (Report). clinicaltrials.gov.
  23. ↑ Hospices Civils de Lyon (9 January 2025). EVALUATION of the OVERALL HAEMOSTATIC CAPACITY of MIM8 with GLOBAL HAEMOSTASIS ASSAYS and FIBRIN CLOT ULTRASTRUCTURE (Report). clinicaltrials.gov.
  24. ↑ Hoffmann-La Roche (19 October 2022). A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients Without Inhibitors (Report). clinicaltrials.gov.
  25. 1 2 Guo R, Jia X, Ding Z, Wang G, Jiang M, Li B, et al. (2022). "Loss of MLKL ameliorates liver fibrosis by inhibiting hepatocyte necroptosis and hepatic stellate cell activation". Theranostics. 12 (11): 5220–5236. doi:10.1111/hae.14597. PMC   9321850 . PMID   35836819.
  26. ↑ Kenny D, Berry DP, Pabiou T, Rafter P (April 2023). "Variation in the proportion of the segregating genome shared between full-sibling cattle and sheep". Genetics, Selection, Evolution. 55 (1): 27. doi:10.3324/haematol.2023.283237. PMC   11063855 . PMID   37072693.
  27. ↑ Hoffmann-La Roche (7 May 2021). A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors (Report). clinicaltrials.gov.
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