COMMODORE 2
Trial question
Is crovalimab noninferior to eculizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 204
204 patients (92 female, 112 male).
Inclusion criteria: patients with paroxysmal nocturnal hemoglobinuria naïve to complement inhibition.
Key exclusion criteria: current/previous treatment with a complement inhibitor; history of allogeneic bone marrow transplantation; history of N. meningitidis infection in the past 6 months; splenectomy in the past 6 months.
Interventions
N=135 crovalimab (weight-based loading IV dose on day 1, followed by SC doses on days 2, 8, 15, and 22 and maintenance dose every 4 weeks starting from day 29).
N=69 eculizumab (loading dose of 600 mg on days 1, 8, 15, and 22, followed by maintenance dose of 900 mg on day 29 and every 2 weeks thereafter until 24 weeks).
Primary outcome
Proportion of patients with hemolysis control through week 25
79.3%
79%
79.3 %
59.5 %
39.6 %
19.8 %
0.0 %
Crovalimab
Eculizumab
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in the proportion of patients with hemolysis control through week 25 (79.3% vs. 79%; OR 1, 95% CI 0.6 to 1.8).
Secondary outcomes
No significant difference in the proportion of patients with transfusion avoidance through week 25 (65.7% vs. 68.1%; WD -2.8, 95% CI -15.7 to 11.1).
Borderline significant decrease in the proportion of patients with breakthrough hemolysis through week 25 (10.4% vs. 14.5%; WD -3.9, 95% CI 14.8 to 5.3).
No significant difference in the proportion of patients with hemoglobin stabilization through week 25 (63.4% vs. 60.9%; WD 2.2, 95% CI -11.4 to 16.3).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with paroxysmal nocturnal hemoglobinuria naïve to complement inhibition, crovalimab was noninferior to eculizumab with respect to the proportion of patients with hemolysis control through week 25.
Reference
Alexander Röth, Guangsheng He, Hongyan Tong et al. Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition. Am J Hematol. 2024 Jun 17. Online ahead of print.
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