Crovalimab Demonstrates Noninferiority to Eculizumab in Phase 3 COMMODORE 2 Trial in PNH

Treatment with crovalimab led to disease control through transfusion avoidance and control of hemolysis in patients with paroxysmal nocturnal hemoglobinuria who have not been previously treated with complement inhibitors.

Treatment with crovalimab led to disease control through transfusion avoidance and control of hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have not been previously treated with complement inhibitors, meeting the co-primary end points of the phase 3 COMMODORE 2 trial (NCT04434092).1

Prior efficacy and safety data from the phase 3 COMMODORE 1 trial (NCT04432584) supported the favorable benefit-risk profile of crovalimab in patients with PNH who switched from currently approved C5 inhibitors to crovalimab.

Findings from both studies will be submitted to global regulatory agencies and presented at an upcoming medical meeting.

“People with PNH may benefit from more options to achieve robust disease control with less frequent treatment intervals,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a press release. “As the first global phase 3 data for crovalimab, these results emphasize its potential to address these needs. We look forward to submitting these data to regulatory authorities, bringing us one step closer to making crovalimab available for people with PNH around the world.”

PNH is a rare and life-threatening blood condition in which red blood cells are destroyed by the complement system, resulting in anemia, fatigue, blood clots, and kidney disease. C5 inhibitors can be effective in treating PNH; however, the current standard of care, eculizumab (Soliris), is given intravenously every 2 weeks.

Crovalimab is a novel, investigational anti-C5 recycling monoclonal antibody, administered subcutaneously every 4 weeks. The agent was designed to be recycled within the circulation, leading to sustained complement inhibition through low dose, subcutaneous administration, potentially providing patients with an at-home administration option. Moreover, the agent binds to a different C5 binding site from available treatments, which may provide an effective option for patients with specific C5 gene mutations who do not respond to standard therapy.

COMMODORE 2 is a phase 3, randomized, open-label study evaluating the efficacy and safety of crovalimab vs eculizumab in patients with PNH who have not been previously treated with C5 inhibitors.

The co-primary end points of the study are the degree of transfusion avoidance and control of hemolysis. Eligible patients were randomly assigned in a 2:1 fashion to receive subcutaneous crovalimab every 4 weeks or intravenous eculizumab every 2 weeks. Patients under the age of 18 years were enrolled in a non-randomized treatment arm and received subcutaneous crovalimab every 4 weeks.

COMMODORE 1 is a phase 3, randomized, open-label study evaluating the safety of crovalimab in patients with PNH switching from currently approved C5 inhibitors.

The objectives of the study were to establish the safety, tolerability, pharmacokinetics, and pharmacodynamic properties of crovalimab. The study enrolled patients with PNH 18 years of age or older who were being treated with eculizumab. In a non-randomized arm, the study enrolled patients under the age of 18 years currently treated with eculizumab at approved or off-label doses, those currently treated with ravulizumab-cwvz (Ultomiris), and those with known mutations in the C5 gene who do not respond to current therapies.

Positive data from the phase 3 COMMODORE 3 trial (NCT04654468), conducted in China, were presented at the 2022 ASH Annual Meeting.2 Results showed that the mean proportion of patients achieving hemolysis control from weeks 5 through 25 was 78.7% (95% CI, 67.8%-86.6%), and the proportion of patients achieving hemolysis control at week 5 was 72% and remained between 70% and 85%.

Additionally, 51.0% (95% CI, 36.8%-65.1%) of patients reached transfusion avoidance post baseline, which was a statistically significant improvement vs 0% (95% CI, 0.0%-8.7%) in the 24 weeks prior to patients being screened (95% CI, 34.3%-65.1%; P < .0001).

Data from the trial were submitted through China’s Centre for Drug Evaluation Breakthrough Therapy Designation pathway and the submission subsequently received priority review for approval by China’s National Products Administration.

In addition to PNH, crovalimab is being evaluated in other complement-mediated diseases, including atypical hemolytic uremic syndrome and sickle cell disease.

References

  1. Roche announces positive data from global phase III programme for crovalimab in PNH, a rare life-threatening blood condition. News release. Roche. February 7, 2023. Accessed February 7, 2023. https://www.globenewswire.com/news-release/2023/02/07/2602583/0/en/Roche-announces-positive-data-from-global-phase-III-programme-for-crovalimab-in-PNH-a-rare-life-threatening-blood-condition.html
  2. Liu H, Zhang F, Jia 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). Blood. 2022;140(suppl 1):714-716. doi:10.1182/blood-2022-162452