Roche announces positive Phase 3 data for crovalimab in PNH
If approved by regulators, crovalimab could take on AstraZeneca’s blockbuster drug Soliris (eculizumab): which was the first drug approved by the FDA and EMA to treat PNH and is currently used in nearly 50 countries. The drug, acquired via the takeover of Alexion, boasted $1.9bn in revenue in 2021 across all indications.
Now, the new Roche data shows that crovalimab could be given as an injection every four weeks, compared to every two weeks for eculizumab.
Phase 3 data
The Phase 3 Commodore 2 study is evaluating the efficacy and safety of crovalimab in people with paroxysmal nocturnal hemoglobinuria (PNH) who have not been previously treated with complement inhibitors.
Announcing the new data this morning, Roche says the study met 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, a current standard of care’, which is given intravenously every two weeks.
Meanwhile, a separate Phase III study, entitled Commodore 1, has presented efficacy and safety data in people with PNH switching from currently approved C5 inhibitors to crovalimab: with this data supporting the 'favorable benefit-risk profile of crovalimab, as seen in the pivotal Commodore 2 study'.
“People with PNH may benefit from more options to achieve robust disease control with less frequent treatment intervals,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.
“As the first global phase III data for crovalimab, these results emphasise 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.”
Data from both studies will be submitted to regulatory authorities around the world and presented at an upcoming medical meeting, added Garraway.
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.
C5 inhibitors can be effective in treating the condition. Crovalimab has been engineered to be recycled within the circulation, enabling sustained complement inhibition through low-dose, subcutaneous administration every four weeks.
In addition, it 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 five ongoing Phase III studies: including atypical hemolytic uremic syndrome, sickle cell disease and other complement-mediated diseases.
In December, Roche announced that the Phase 3 Commodore 3 study, undertaken in China, was efficacious in PNH, meeting the co-primary endpoints of transfusion avoidance and haemolysis control. Data from this study has been submitted as part of a drug application to China’s National Medical Products Administration under priority review.
COMMODORE 1 and 2 Phase 3 studies
The COMMODORE 2 study is a Phase III, randomized, open-label study evaluating the efficacy and safety of crovalimab versus eculizumab in people with paroxysmal nocturnal hemoglobinuria (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 ongoing destruction of red blood cells measured by lactate dehydrogenase levels). 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.
The COMMODORE 1 study is a Phase III, randomized, open-label study evaluating the safety of crovalimab in people with PNH switching from currently approved C5 inhibitors. The study’s outcome measures evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic properties of crovalimab.
The study included people (18 years of age or older) currently treated with eculizumab. In a non-randomized arm, the study also included pediatrics (<18 years of age) currently treated with eculizumab, people currently treated with ravulizumab, people currently treated with off-label doses of eculizumab (higher than the approved dose for PNH: more than 900 mg per dose and/or more frequently than every two weeks) or people with known mutations in the C5 gene who do not respond to current therapies.