Crovalimab Shows Non-Inferiority to Current Standard of Care for Paroxysmal Nocturnal Hemoglobinuria

Crovalimab, a novel and investigational anti-C5 recycling monoclonal antibody, achieved disease control and non-inferiority to eculizumab, the current standard of care (SoC) for patients with paroxysmal nocturnal hemoglobinuria (PNH), according to results from the COMMODORE 2 study. Crovalimab was found to be safe and effective for patients who have not been previously treated with a complementary inhibitor.

Data from the COMMODORE 2 study show that crovalimab can control hemolysis, defined as the ongoing destruction of red blood cells as measured by lactate dehydrogenase levels, and help patients to avoid blood transfusion.

“People with PNH may benefit from more options to achieve robust disease control with less frequent treatment intervals,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, in a press release. “As the first global phase 3 data for crovalimab, these results emphasize its potential to address these needs.”

The novel antibody was designed to block the complement system, which functions as the body’s first line of defense against infection. Although the complement system is a vital part of the immune system, it destroys the red blood cells of patients with PNH. This results in anemia, fatigue, and possibly life-threatening conditions, such as blood clots and kidney disease.

Crovalimab binds to C5 sites and is circulated and recycled throughout the compliment system. Crovalimab is even able to bind to the C5 sites created by previous, unsuccessful treatments, which enables crovalimab to be an effective treatment option for people who were nonresponsive to other therapies, according to Genentech.

The COMMADORE 2 trial enrolled patients aged 18 years and older who have PNH and have not been previously treated with another C5 inhibitor, such as eculizumab. The patients were randomized in a 2:1 ratio, with 1 arm receiving subcutaneous (SC) crovalimab every 4 weeks, the other receiving intravenous (IV) eculizumab every 2 weeks.

Researchers previously performed the COMMODORE 1 study, a global, randomized, open-label, phase 3 trial that evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamic properties of crovalimab in patients who have previously taken an approved C5 inhibitor.

In both COMMODORE phase 3 trials, crovalimab was evaluated for patients under 18 years of age. The COMMODORE 2 study evaluated the efficacy and safety of SC crovalimab administered every 4 weeks, and the COMMODORE 1 study evaluated crovalimab for patients previously on eculizumab, ravulizumab, off-label doses of eculizumab, or with other C5 gene mutations.

Crovalimab is being evaluated for PNH, atypical hemolytic uremic syndrome, sickle cell disease, and various complement-mediated diseases in 5 ongoing phase 3 trials as part of a larger clinical development program. The results of the COMMODORE studies will be submitted to global regulatory authorities.

“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,” Garraway said in the press release.

Reference

Genentech Announces Positive Data From Global Phase III Program for Crovalimab in PNH, a Rare, Life-Threatening Blood Condition. Genentech. February 6, 2023. Accessed on February 7, 2023. https://www.gene.com/media/press-releases/14982/2023-02-06/genentech-announces-positive-data-from-g