Crovalimab

Last updated

Crovalimab
Monoclonal antibody
Type Whole antibody
Source Humanized
Target Complement component 5 (C5)
Clinical data
Trade names Piasky
Other namescrovalimab-akkz
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Subcutaneous, intravenous
Drug class Complement inhibitor
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C6430H9974N1726O2026S46
Molar mass 145349.34 g·mol−1

Crovalimab, sold under the brand name Piasky, is a monoclonal antibody used for the treatment of people with paroxysmal nocturnal hemoglobinuria. [1] It is a complement component 5 (C5) inhibitor. [1] [5]

Contents

Crovalimab was approved for use in China in February 2024, [6] in Japan in April 2024, [7] in the United States in June 2024 and in the European Union in August 2024. [3] [4] [2] It was developed and is marketed by Roche/Genentech.

Medical uses

In the US, crovalimab is indicated for the treatment of people aged 13 years of age and older with paroxysmal nocturnal hemoglobinura and body weight of at least 40 kilograms (88 lb). [1] [8]

Adverse effects

The US FDA label for crovalimab contains a boxed warning about the increased risk of Neisseria meningitidis infection, which can be life-threatening. A recent meningococcal vaccination is strongly advised. [1]

History

Clinical trials

Three phase III clinical trials have evaluated crovalimab in both people who were C5 inhibitor–naive and those switching to crovalimab from other C5 inhibitors. [9]

COMMODORE 1 [10] is a phase III randomized clinical trial comparing crovalimab vs eculizumab in people with paroxysmal nocturnal hemoglobinuria treated with C5 inhibitors. [11] COMMODORE 1 examines the safety, tolerability and pharmacokinetic/pharmacodynamic properties of crovalimab in PNH patients switching from eculizumab. The study showed that crovalimab maintained disease control in PNH patients switching from eculizumab. [11] [12]

COMMODORE 2 [13] is a phase III randomized trial comparing crovalimab vs eculizumab in people with paroxysmal nocturnal hemoglobinuria who are naive to C5 inhibitor treatment. [14] COMMODORE 2 was positive for its co-primary endpoints, transfusion avoidance and hemolysis control (measured lactate dehydrogenase levels) which are disease control indicators, and its data shows crovalimab is non-inferior to eculizumab. [15] [14] [16] [17]

COMMODORE 3 [18] is a phase III single-arm trial run in China, studying crovalimab in C5 inhibitor-naive people with paroxysmal nocturnal hemoglobinuria. [19] COMMODORE 3 assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of crovalimab in people with C5-naive paroxysmal nocturnal hemoglobinuria. The study met the co-primary efficacy endpoints of haemolysis control and transfusion avoidance. [19] [20]

Society and culture

Crovalimab was approved for use in China in February 2024, [6] and in Japan in April 2024. [7] [21]

Crovalimab was approved for medical use in the United States in June 2024. [2] [8]

In June 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Piasky, intended as monotherapy for the treatment of people twelve years of age or older with a weight of 40 kilograms (88 lb) and above with paroxysmal nocturnal haemoglobinuria. [3] [22] The applicant for this medicinal product is Roche Registration GmbH. [3] Crovalimab was approved for medical use in the European Union in August 2024. [3] [4]

Names

Crovalimab is the international nonproprietary name. [23]

Research

Crovalimab is the subject of five phase III studies for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS). It is also being investigated for the treatment of sickle cell disease and other conditions. [24]

Related Research Articles

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<span class="mw-page-title-main">Paroxysmal nocturnal hemoglobinuria</span> Blood disease in which red blood cells are attacked by the immune system

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation. Research suggests that PNH thrombosis is caused by both the absence of GPI-anchored complement regulatory proteins on PNH platelets and the excessive consumption of nitric oxide (NO).

<span class="mw-page-title-main">Factor D</span> Class of enzymes

Factor D is a protein which in humans is encoded by the CFD gene. Factor D is involved in the alternative complement pathway of the complement system where it cleaves factor B.

Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica. In people with paroxysmal nocturnal hemoglobinuria, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first medication approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion. It is a humanized monoclonal antibody functioning as a terminal complement inhibitor. It binds to the complement C5 protein and inhibits activation of the complement system, a part of the body's immune system. This binding prevents the breakdown of red blood cells in the bloodstream in people with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

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<span class="mw-page-title-main">CD55 deficiency</span> Medical condition

CD55deficiency, also called DAF deficiency or CHAPLE syndrome, is a rare genetic disorder of the immune system. CHAPLE stands for "CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and severe protein-losing enteropathy (PLE)." The disorder usually manifests in childhood and can be life-threatening. This condition was described by Özen, et al. in 2017.

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Pegcetacoplan, sold under the brand name Empaveli, among others, is a medication used to treat paroxysmal nocturnal hemoglobinuria and geographic atrophy of the retina. Pegcetacoplan is a complement inhibitor.

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<span class="mw-page-title-main">Sucrose lysis test</span>

The sucrose lysis test is a diagnostic laboratory test used for diagnosing paroxysmal nocturnal hemoglobinuria (PNH), as well as for hypoplastic anemias and any hemolytic anemia with an unclear cause. The test works by using sucrose, which creates a low ionic strength environment that allows complement to bind to red blood cells. In individuals with PNH, some red blood cells are especially vulnerable to lysis caused by complement. The test may also produce suspicious results in other hematologic conditions, including megaloblastic anemia and autoimmune hemolytic anemia. False-negative results can occur when complement activity is absent in the serum. A simpler alternative called the sugar water test also involves mixing blood with sugar and observing for hemolysis, using the same principle as the sucrose lysis test.

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References

  1. 1 2 3 4 5 "Piasky- crovalimab injection, solution". DailyMed. 28 June 2024. Retrieved 5 September 2024.
  2. 1 2 3 "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 21 June 2024. Archived from the original on 30 April 2024. Retrieved 21 June 2024.
  3. 1 2 3 4 5 "Piasky EPAR". European Medicines Agency (EMA). 27 June 2024. Retrieved 29 June 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. 1 2 3 "Piasky Product information". Union Register of medicinal products. 26 August 2024. Retrieved 27 August 2024.
  5. ↑ Röth, Alexander; Nishimura, Jun-ichi; Nagy, Zsolt; Gaàl-Weisinger, Julia; Panse, Jens; Yoon, Sung-Soo; et al. (19 March 2020). "The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria". Blood. 135 (12): 912–920. doi:10.1182/blood.2019003399. PMC   7082616 . PMID   31978221.
  6. 1 2 "Crovalimab Approved in China as the First Country, for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)". chugai-pharm.co.jp. 8 February 2024. Archived from the original on 18 April 2024. Retrieved 18 April 2024.
  7. 1 2 "Japan Becomes Second Market to Approve Roche's Piasky". Navlin Daily. 3 April 2024. Archived from the original on 18 April 2024. Retrieved 21 June 2024.
  8. 1 2 "Crovalimab approval letter" (PDF). Archived from the original (PDF) on 25 June 2024. Retrieved 25 June 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ Brodsky RA (March 2020). "A complementary new drug for PNH". Blood. 135 (12): 884–885. doi:10.1182/blood.2020004959. PMC   8555420 . PMID   32191798.
  10. ↑ A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Safety, Pharmacokinetics, Pharmacodynamic And Efficacy of Crovalimab Versus Eculizumab In Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors (Report). 6 June 2024. Archived from the original on 15 May 2024. Retrieved 21 June 2024.
  11. 1 2 Scheinberg, Phillip; Cle, Diego; Edwards, John; Giai, Valentina; Hus, Marek; Kim, Jin Seok; et al. (8 August 2023). "S183: Phase III Randomized, Multicenter, Open-Label COMMODORE 1 Trial: Comparison of Crovalimab vs Eculizumab in Complement Inhibitor-Experienced Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)". HemaSphere. 7 (S3): e45540d8. doi: 10.1097/01.HS9.0000967644.45540.d8 . PMC   10428303 .
  12. ↑ "The phase III randomized, multicenter COMMODORE 1 trial: comparison of crovalimab vs eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH)". Medically. 26 October 2023. Archived from the original on 21 June 2024. Retrieved 21 June 2024.
  13. ↑ A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors (Report). 15 May 2024. Archived from the original on 17 May 2024. Retrieved 21 June 2024.
  14. 1 2 Clarkson DM, Phillips CI (November 1976). "Lens extraction with ultrasound. Experiments in rabbits". The British Journal of Ophthalmology. 60 (11): 759–64. doi: 10.1136/bjo.60.11.759 . PMC   1042834 . PMID   1009054.
  15. ↑ Kulasekararaj, Austin; He, Guangsheng; Munir, Talha; Pu, Jeffrey; Risitano, Antonio; Röth, Alexander; et al. (5 November 2020). "Trial in Progress: The Phase III, Randomized, Open-Label, Multicenter COMMODORE 2 Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria Not Previously Treated with Complement Inhibitors". Blood. 136 (Supplement 1): 34. doi: 10.1182/blood-2020-136647 . S2CID   234740758.
  16. ↑ "The phase III, randomized COMMODORE 2 trial: results from a multicenter study of crovalimab vs eculizumab in paroxysmal nocturnal hemoglobinuria (PNH) patients naive to complement inhibitors". Medically. 9 June 2023. Archived from the original on 21 June 2024. Retrieved 21 June 2024.
  17. ↑ Röth A, He G, Tong H, Lin Z, Wang X, Chai-Adisaksopha C, et al. (June 2024). "Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition". American Journal of Hematology. 99 (9): 1768–1777. doi: 10.1002/ajh.27412 . PMID   38884175.
  18. ↑ A Phase III, Multicenter, Single Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition (Report). 31 May 2024. Archived from the original on 25 June 2024. Retrieved 21 June 2024.
  19. 1 2 Liu, Hui; Xia, Linghui; Weng, Jianyu; Zhang, Fengkui; He, Chuan; Gao, Sujun; et al. (15 November 2022). "Results from the First Phase 3 Crovalimab (C5 Inhibitor) Study (COMMODORE 3): Efficacy and Safety in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)". Blood. 140 (Supplement 1): 714–716. doi: 10.1182/blood-2022-162452 . S2CID   254397884.
  20. ↑ "Six-Month Crovalimab Extension in the Phase III COMMODORE 3 Study: Updated Efficacy and Safety Results in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria". Medically. 9 June 2023. Archived from the original on 21 June 2024. Retrieved 21 June 2024.
  21. ↑ Dhillon S (May 2024). "Crovalimab: First Approval". Drugs. 84 (6): 707–716. doi:10.1007/s40265-024-02032-5. PMID   38740735.
  22. ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024". European Medicines Agency. 28 June 2024. Archived from the original on 12 July 2024. Retrieved 12 July 2024.
  23. ↑ World Health Organization (2019). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1). hdl: 10665/330896 .
  24. ↑ "Genentech Announces Positive Data From Global Phase III Program for Crovalimab in PNH, a Rare, Life-Threatening Blood Condition". Genentech (Press release). 6 February 2023. Archived from the original on 12 January 2024. Retrieved 13 January 2024.
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