NEW ORLEANS, La.—Crovalimab may be safe and effective in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to a single-arm, multicenter trial.
The study results demonstrated that the average number of patients reaching hemolysis control was about 79%. By week 3, average lactate dehydrogenase 1.5 times the upper limit of normal was achieved and maintained through week 25, reported Camelia Sima of Genentech, Inc.
Other data looked at the number of patients with transfusion avoidance within the 24 weeks before screening compared with baseline through week 25 and showed that there was a statistically significant difference at the 2-sided 5% type 1 error phase (P <.0001).
The findings were presented at the 64th ASH Annual Meeting and Exposition from December 10 to 13, 2022.
Read more about PNH epidemiology
“In China and many other countries, the lack of access to effective treatment for PNH, including C5 inhibitors, has resulted in a high unmet need in people living with this disease. Crovalimab is a novel anti-C5 recycling monoclonal antibody. It’s long half life, its solubility, and bioavailability support the development of a high-concentration formulation, enabling infrequent subcutaneous delivery at low volume,” said Sima.
“In the global phase 1/2 COMPOSER study, crovalimab showed rapid and sustained terminal complement activity inhibition in patients with PNH who were complement inhibitor-naive or switched from eculizumab. COMMODORE 3 is a phase 3, open-label, multicenter, single-arm trial of crovalimab in complement inhibitor-naive patients with PNH in China,” she added.
The researchers evaluated 51 Chinese patients with PNH. At baseline, median age was 31 years. All participants were at least 12 years of age, weighed 40 kg or more, had at least 4 packed red blood cell transfusions 1 year before screening, and had lactate dehydrogenase 2 or more times the upper limit of normal. Patients who were previously treated with inhibitor therapy were excluded from the study.
Only 2% of the cohort had myelodysplastic syndrome, and 37% had been previously diagnosed with aplastic anemia.
Patients were treated with crovalimab based on a weight-based dosing schedule, which included the initial loading dose and subcutaneous maintenance doses. The loading dose consisted of an intravenous dose on day 1, and 4 weekly subcutaneous doses beginning on day 2. The maintenance doses were administered every 4 weeks beginning with week 5. After 24 weeks, the researchers continued crovalimab therapy in patients with clinical benefit.
From baseline through week 25, the difference in the number of patients who had transfusion avoidance and from weeks 5 through 25, the average amount of patients with hemolysis control compared with 24 weeks before screening were the primary end points.
Change in fatigue, breakthrough hemolysis, and hemoglobin stabilization were the secondary efficacy endpoints. Immunogenicity and safety were also assessed.
There was a decline in the average number of packed red blood cell units transfused for each patient as indicated by the shift from 10.8 during the 24 weeks before screening to 4.6 from baseline through week 25, with a mean decrease of 6.1 in the number of units transfused for each patient.
Notably, 1 patient discontinued their participation in the investigation early on but had relative breakthrough hemolysis, while 1 patient had breakthrough hemolysis. More than one-half of the cohort reached hemoglobin stabilization.
Other data showed that FACIT-fatigue scores had clinically substantial improvement by week 2, which was maintained through week 17.
Notably, none of the cohort discontinued their participation in the student due to adverse events. A grade 5 adverse event, or subdural hematoma following a fall, was reported in 1 patient but this was not associated with the treatment.
Weight gain and upper respiratory tract infection were reported in at least 10% of patients.
Just over 30% of patients had treatment-emergency antidrug antibodies. None of the patients had neutralizing antibodies.
The drug did not show safety or efficacy among individuals between 12 to 18 years of age.
“The results demonstrated that crovalimab is an efficacious and well-tolerated therapy for patients with PNH. Owing to its every-4-weeks low-volume subcutaneous dosing regiment, with the option for self-administration, crovalimab has the potential to reduce the burden of treatment for this life-long disease,” Sima concluded.
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). 64th ASH Annual Meeting and Exposition. New Orleans, LA; December 10-13, 2022.