Crovalimab

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Crovalimab
Monoclonal antibody
Type?
TargetParoxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), sickle cell disease
Clinical data
Trade namesPiasky
Routes of
administration		Subcutaneous
Drug classComplement inhibitor
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
UNII
KEGG

Crovalimab (trade name Piasky) is an C5 inhibiting monoclonal antibody under investigation by Roche/Genentech for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).[1][2][3][4][5]

Following an initial i.v. loading dose, crovalimab is administered once every 4 weeks as a subcutaneous injection by the patient themselves or by a caregiver.[1][2] Administration can also be done in the clinic if self-injection is not desired by the doctor or the patient.[1][2]

Crovalimab is the subject of five Phase III studies for PNH and atypical hemolytic uremic syndrome (aHUS). It is also being investigated for the treatment of sickle cell disease and other conditions.[6]

Clinical trials

Three Phase 3 clinical trials have evaluated crovalimab in both patients who were C5 inhibitor–naive and those switching to crovalimab from other C5 inhibitors.

COMMODORE 1[7] is a Phase III randomized clinical trial comparing crovalimab vs eculizumab in PNH patients treated with C5 inhibitors.[4] 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.

COMMODORE 2[8] is a Phase III randomized trial comparing crovalimab vs eculizumab in people with PNH who are naive to C5 inhibitor treatment.[5] 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.

COMMODORE 3[9] is a Phase III single-arm trial run in China, studying crovalimab in C5 inhibitor-naive patients with PNH.[2] COMMODORE 3 assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of crovalimab in c5-naive PNH patients. The study met the co-primary efficacy endpoints of haemolysis control and transfusion avoidance.

Approval

Crovalimab was approved for use in China in February 2024[10] and in Japan in April 2024.[11]

References

  1. ^ a b c Kulasekararaj, Austin; He, Guangsheng; Munir, Talha; Pu, Jeffrey; Risitano, Antonio; Röth, Alexander; Sima, Camelia S.; Appius, Anita; Sostelly, Alexandre; Sreckovic, Sasha; Vignal, Charlotte; Nishimura, Jun-Ichi (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.
  2. ^ a b c d Liu, Hui; Xia, Linghui; Weng, Jianyu; Zhang, Fengkui; He, Chuan; Gao, Sujun; Jia, Jinsong; Chang, Alice C.; Lundberg, Pontus; Sima, Camelia S.; Shi, Jane; Xiao, Zhenyu; Zhang, Yuchen; Zhang, Zilu; Fu, Rong (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.
  3. ^ Röth, Alexander; Nishimura, Jun-ichi; Nagy, Zsolt; Gaàl-Weisinger, Julia; Panse, Jens; Yoon, Sung-Soo; Egyed, Miklos; Ichikawa, Satoshi; Ito, Yoshikazu; Kim, Jin Seok; Ninomiya, Haruhiko; Schrezenmeier, Hubert; Sica, Simona; Usuki, Kensuke; Sicre de Fontbrune, Flore; Soret, Juliette; Sostelly, Alexandre; Higginson, James; Dieckmann, Andreas; Gentile, Brittany; Anzures-Cabrera, Judith; Shinomiya, Kenji; Jordan, Gregor; Biedzka-Sarek, Marta; Klughammer, Barbara; Jahreis, Angelika; Bucher, Christoph; Peffault de Latour, Régis (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.
  4. ^ a b "PHASE III RANDOMIZED, MULTICENTER, OPEN-LABEL COMMODORE 1 TRIAL: COMPARISON OF CROVALIMAB VS ECULIZUMAB IN COMPLEMENT INHIBITOR-EXPERIENCED PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)". European Hematology Association (EHA) 2023: Annual Meeting Abstracts. S183 – via EHA Library.
  5. ^ a b "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". European Hematology Association (EHA) 2023: Annual Meeting Abstracts. S181 – via EHA Library.
  6. ^ "Genentech Announces Positive Data From Global Phase III Program for Crovalimab in PNH, a Rare, Life-Threatening Blood Condition". Genentech Press Release.
  7. ^ NCT04432584
  8. ^ NCT04434092
  9. ^ NCT04654468
  10. ^ "Crovalimab Approved in China as the First Country, for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)". chugai-pharm.co.jp. February 8, 2024.
  11. ^ "Japan Becomes Second Market to Approve Roche's Piasky". navlindaily.com. April 3, 2024.
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