RARE Daily

Roche Reports Positive Results from Phase 3 PNH Study of Crovalimab

December 12, 2022

Roche reported positive new data from the phase 3 COMMODORE 3 study in China, demonstrating that crovalimab, a novel anti-C5 recycling monoclonal antibody, is efficacious and well-tolerated in people with the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH).

Photo: Levi Garraway, Roche’s chief medical officer and head of global product development

The company said the study met its co-primary efficacy endpoints of transfusion avoidance (TA) and hemolysis control, demonstrating that participants with PNH, who have not been treated previously with complement inhibitors and who received subcutaneous crovalimab injections every four weeks, achieved disease control. The data were presented at the American Society of Hematology (ASH) congress.

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare and life-threatening blood condition, where red blood cells are targeted and destroyed by the complement system—part of the innate immune system—causing symptoms such as anemia, fatigue, blood clots, and kidney disease.

Crovalimab is an experimental, novel, anti-C5 recycling monoclonal antibody designed to block the complement system, a vital part of the innate immune system that acts as the body’s first line of defense against infections. Crovalimab has been engineered to address the medical needs of people living with complement-mediated diseases and overcome some of the challenges of currently available treatment options. Similar to currently approved C5 inhibitors, crovalimab binds to C5, blocking the last step of the complement cascade. However, crovalimab is also recycled into circulation, enabling rapid and sustained complement inhibition, which may potentially overcome the problem of incomplete C5 inhibition with currently available treatments.

Crovalimab’s recycling action also enables low dose subcutaneous administration every four weeks, potentially removing the need for regular, time-consuming intravenous infusions. 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.

“As crovalimab has been developed to be taken subcutaneously and infrequently, with the option to self-administer, it has the potential to become an important treatment option for people everywhere living with paroxysmal nocturnal hemoglobinuria,” said Levi Garraway, Roche’s chief medical officer and head of global product development.

The COMMODORE 3 study included data from 51 participants with PNH, who received crovalimab subcutaneously every four weeks during the primary study period. Results showed that the co-primary efficacy endpoints of hemolysis control and TA, indicators of disease control, were met. The mean proportion of participants with hemolysis control from week five through to week 25 was 78.7 percent. The difference between the proportion of participants with TA within 24 weeks prior to screening (0 percent) and the proportion of participants with TA from baseline through to week 25 (51 percent) was statistically significant. TA is defined as people who become transfusion-free and do not require transfusion per protocol-specified guidelines. Blood transfusion requirements are important clinical measures of hemolysis caused by complement dysregulation in PNH.

Data from the COMMODORE 3 study have been submitted via China’s Centre for Drug Evaluation Breakthrough Therapy Designation pathway. This submission has been accepted under Priority Review for approval consideration in PNH by China’s National Medical Products Administration. As the availability of C5 inhibitors is extremely limited in China, there remains a high clinical need for people living with PNH there.

Roche is conducting five ongoing global phase 3 studies of crovalimab. It is being evaluated in paroxysmal nocturnal hemoglobinuria, atypical hemolytic uraemic syndrome, sickle cell disease, and other complement mediated diseases.

Author: Rare Daily Staff

Stay Connected

Sign up for updates straight to your inbox.