Crovalimab Shows ‘Positive Benefit-Risk Profile’ in PNH

New results from the phase III COMMODORE 2 trial show that in patients with paroxysmal nocturnal hemoglobinuria (PNH) not previously treated with C5 complement inhibitors, crovalimab has efficacy noninferior to eculizumab.

Lead author Alexander Röth, MD, of the West German Cancer Center at the University Hospital Essen in Germany, added that “[t]hese data demonstrate the positive benefit-risk profile of crovalimab.” The study was published recently in the American Journal of Hematology.

This phase III, randomized, open-label, global multicenter trial involved 204 patients, 135 of whom were randomized to crovalimab and 69 to eculizumab. All had lactate dehydrogenase (LDH) at least twice the upper limit of normal (ULN) and underwent a primary treatment period of 24 weeks.

For its primary endpoints, the trial assessed what proportions of patients achieved hemolysis control, defined as having centrally assessed LDH of 1.5 times ULN or less, and transfusion avoidance. In both, crovalimab had performance noninferior to eculizumab, with hemolysis control achieved by 79.3% of the cohort (vs 79.0% of the eculizumab cohort) and transfusion avoidance by 65.7% (vs 68.1%).

Among secondary endpoints in the trial, breakthrough hemolysis was experienced by 10.4% of the crovalimab patients compared with 14.5% of the eculizumab patients. Hemoglobin stabilization was achieved by 63.4% of crovalimab patients compared with 60.9% of eculizumab patients. Both cohorts saw a clinically meaningful improvement in Functional Assessment of Chronic Illness Therapy-Fatigue score.

Regarding safety profiles, these were similar between the two agents. Moreover, there were no instances of meningococcal infection.

Overall, the patients who received crovalimab had continuous complete terminal complement activity inhibition. Dr. Röth also noted that “[m]ost patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab.”

Reference

Röth A, He G, Tong H, 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. doi:10.1002/ajh.27412