The novel C5 inhibitor crovalimab is efficacious and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to research presented at the 2022 ASH Annual Meeting.
The findings are from COMMODORE 3, a phase 3 multicenter single-arm trial, studying crovalimab in C5 inhibitor-naïve patients with PNH in China (ClinicalTrials.gov Identifier: NCT04654468).
Key inclusion criteria for C5 inhibitor-naïve patients with PNH were age ≥12 years, weight ≥40 kg, lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and ≥4 packed red blood cell transfusions 1 year before screening.
Patients were given crovalimab according to a weight-based dosing schedule. An intravenous dose loading dose was administered on Day 1, followed by 4 weekly subcutaneous doses starting from Day 2 and subcutaneous maintenance doses every 4 weeks starting from Week 5.
The coprimary endpoints of the study were mean proportion of patients with hemolysis control (defined as LDH ≤1.5 × ULN) from Week 5 through Week 25 and difference in proportion of patients who had transfusion avoidance from baseline through Week 25 vs within 24 weeks prior to screening.
A total of 51 patients (57% female and 43% male), with a median age of 31 years (range, 15-58; aged ≤18 years, n=3) participated in the study. The median time from PNH diagnosis was 7.1 years (range, 0.7-18.2). A history of PNH-relevant conditions were observed in 39% of patients (aplastic anemia, n=19 [37%]; myelodysplastic syndrome, n=1 [2%]). The mean LDH (× ULN) at baseline was 9.3±2.8. Within 1 year prior to screening, patients received a median of 16 packed red blood cell (pRBC) units (range, 8–51).
At the data cutoff on February 10, 2022, the investigators found both coprimary endpoints were met. They reported the mean proportion of patients achieving hemolysis control was 78.7% (95% CI, 67.8-86.6), with a mean LDH of ≤ 1.5 × ULN reached by Week 3 and sustained through Week 25. They observed a significant difference between proportion of patients with transfusion avoidance from baseline through Week 25 vs within 24 weeks prior to screening (51% vs 0%; P <.0001).
The team found the mean number of pRBC units transfused per patient decreased from 10.8±6.6 during the 24 weeks prior to screening to 4.6±6.7 from baseline through Week 25. Among patients who did not achieve transfusion avoidance (n=25), the investigators reported mean number of pRBC units transfused per patient was 13.4±6.5 during the 24 weeks prior to screening and 9.4±6.8 from baseline through Week 25.
The investigators reported no adverse events leading to treatment discontinuation and the occurrence of a grade 5 adverse event deemed not-treatment related (subdural hematoma after a fall). They found 31% of patients developed treatment-emergent anti-drug antibodies, but no patients developed neutralizing antibodies.
“In conclusion, the study COMMODORE 3 met both coprimary efficacy endpoints of hemolysis control and transfusion avoidance, with no new safety signal signals, in a study population that is reflective of a general PNH population without access to complement inhibitors,” the study presenter concluded.
Disclosure: This research was supported by F. Hoffmann-La Roche Ltd. Please see the original reference for a full list of disclosures.
Liu H, Xia L, Weng J, et al. 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). Presented at ASH 2022. December 10-13, 2022. Abstract 293.