crovalimab

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crovalimab

GtoPdb Ligand ID: 12790

Synonyms: crovalimab-akkz | Piasky® | RG-6107 | RG6107 | Senkai® (China) | SKY59

crovalimab is an approved drug (China NMPA, FDA & EMA (2024))

Comment: Crovalimab (SKY59/RG6107) is a long-acting anti-C5 recycling monoclonal antibody [2,6]. The antibody is engineered to bind C5 in a pH-dependent manner. It binds strongly to C5 in the plasma, but in the acidic conditions within the endosome the antibody-C5 immune complex dissociates. The free antibody is re-cycled and can bind more plasma C5, to provide sustained complement inhibition. The C5 released in the endosome is trafficked to the lysosome for degradation. Crovalimab is proposed as a treatment for complement-mediated disorders such as paroxysmal nocturnal hemoglobinuria (PNH) [5] and Lupus nephritis.

References
1. Dhillon S. (2024) Crovalimab: First Approval. Drugs, 84 (6): 707-716. [PMID:38740735]
2. Fukuzawa T, Sampei Z, Haraya K, Ruike Y, Shida-Kawazoe M, Shimizu Y, Gan SW, Irie M, Tsuboi Y, Tai H et al.. (2017) Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. Sci Rep, 7 (1): 1080. [PMID:28439081]
3. Liu H, Xia L, Weng J, Zhang F, He C, Gao S, Jia J, Chang AC, Lundberg P, Shi J et al.. (2023) Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study. Am J Hematol, 98 (9): 1407-1414. [PMID:37421604]
4. Röth A, He G, Tong H, Lin Z, Wang X, Chai-Adisaksopha C, Lee JH, Brodsky A, Hantaweepant C, Dumagay TE et al.. (2024) Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition. Am J Hematol, 99 (9): 1768-1777. [PMID:38884175]
5. Röth A, Nishimura JI, Nagy Z, Gaàl-Weisinger J, Panse J, Yoon SS, Egyed M, Ichikawa S, Ito Y, Kim JS et al.. (2020) The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria. Blood, 135 (12): 912-920. [PMID:31978221]
6. Sampei Z, Haraya K, Tachibana T, Fukuzawa T, Shida-Kawazoe M, Gan SW, Shimizu Y, Ruike Y, Feng S, Kuramochi T et al.. (2018) Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. PLoS One, 13 (12): e0209509. [PMID:30592762]

References

1. Dhillon S. (2024)
Crovalimab: First Approval.
Drugs, 84 (6): 707-716. [PMID:38740735]

2. Fukuzawa T, Sampei Z, Haraya K, Ruike Y, Shida-Kawazoe M, Shimizu Y, Gan SW, Irie M, Tsuboi Y, Tai H et al.. (2017)
Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases.
Sci Rep, 7 (1): 1080. [PMID:28439081]

3. Liu H, Xia L, Weng J, Zhang F, He C, Gao S, Jia J, Chang AC, Lundberg P, Shi J et al.. (2023)
Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study.
Am J Hematol, 98 (9): 1407-1414. [PMID:37421604]

4. Röth A, He G, Tong H, Lin Z, Wang X, Chai-Adisaksopha C, Lee JH, Brodsky A, Hantaweepant C, Dumagay TE et al.. (2024)
Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.
Am J Hematol, 99 (9): 1768-1777. [PMID:38884175]

5. Röth A, Nishimura JI, Nagy Z, Gaàl-Weisinger J, Panse J, Yoon SS, Egyed M, Ichikawa S, Ito Y, Kim JS et al.. (2020)
The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria.
Blood, 135 (12): 912-920. [PMID:31978221]

6. Sampei Z, Haraya K, Tachibana T, Fukuzawa T, Shida-Kawazoe M, Gan SW, Shimizu Y, Ruike Y, Feng S, Kuramochi T et al.. (2018)
Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody.
PLoS One, 13 (12): e0209509. [PMID:30592762]