Genentech’s C5 Inhibitor Meets Co-Primary Endpoints in Phase 3 Study in PNH

Rare Daily Staff

Roche’s Genentech said its C5 complement inhibitor crovalimab met its co-primary endpoints in a late stage study evaluating its safety and efficacy in people with people with paroxysmal nocturnal hemoglobinuria who have not been previously treated with complement inhibitors.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening blood condition in which red blood cells are destroyed by the complement system. This causes symptoms such as anemia, fatigue, blood clots, and kidney disease.

Crovalimab works by binding to C5, blocking the last step of the complement cascade and is also recycled into circulation, enabling rapid and sustained complement inhibition. Crovalimab’s recycling action also enables low-dose subcutaneous administration every four weeks. In addition, crovalimab binds to a different C5 binding site from current treatments, which has the potential to provide an effective treatment option for people with specific C5 gene mutations, who do not respond to current therapies. Crovalimab is being investigated in a clinical development program including five ongoing Phase III studies. Crovalimab is being evaluated in PNH, atypical hemolytic uremic syndrome, sickle cell disease, and other complement-mediated diseases.

The study met its co-primary efficacy endpoints of transfusion avoidance and control of hemolysis (the ongoing destruction of red blood cells measured by lactate dehydrogenase levels). Results showed that crovalimab, a novel, investigational anti-C5 recycling monoclonal antibody, given as a subcutaneous injection every four weeks, achieved disease control and was non-inferior to eculizumab (Alexion’s Soliris), a current standard of care, which is given intravenously every two weeks.

The COMMODORE 2 study is a phase 3, randomized, open-label study evaluating the efficacy and safety of crovalimab versus eculizumab in people with PNH who have not been previously treated with C5 inhibitors. The study’s co-primary efficacy endpoints measure transfusion avoidance and control of hemolysis. The adults enrolled in the study were randomized in a 2:1 ratio to be treated with either subcutaneous (SC) crovalimab every four weeks or intravenous (IV) eculizumab every two weeks. The participants who were less than 18 years old were included in a non-randomized treatment arm and were treated with SC crovalimab every four weeks.

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

Photo: Levi Garraway, chief medical officer and head of Global Product Development for Genentech