Roche Submits BLA to FDA for Crovalimab, a Once-Monthly Subcutaneous C5 Inhibitor for PNH

On September 6, Genentech, a subsidiary of Roche, announced that the U.S. FDA has accepted the company's Biologics License Application (BLA) for crovalimab (trade name: Corlieva), a novel complement C5 monoclonal antibody, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). If approved, crovalimab will become the first subcutaneous formulation for PNH that requires dosing only once a month, with the option for patients to self-administer.

PNH is a rare and life-threatening blood disease triggered by the destruction of red blood cells by the complement system. Without treatment, patients face a 35% risk of death within five years. Currently, ravulizumab and eculizumab are the only two approved C5-targeted drugs for the treatment of PNH.

Crovalimab is a novel recyclable monoclonal antibody targeting complement C5 that has been engineered by Roche using the continuous monoclonal antibody recycling technology (Smart-Ig). It has a longer duration of C5 neutralization compared to traditional C5 antibodies. Additionally, crovalimab’s binding site differs from existing C5 therapies, offering a new treatment option for PNH patients carrying the R885H mutation.

Source: Roche Official Website

This submission is based on the positive results of two Phase III studies (COMMODORE 1 and COMMODORE 2).

COMMO DORE 1 is a multicenter, randomized, open-label, positive-controlled Phase III clinical trial that evaluated the safety of crovalimab as a substitute for eculizumab or ravulizumab treatment. The primary endpoints of the study were the severity and incidence of adverse events (AEs), injection site reactions, infusion-related reactions, hypersensitivity reactions, and infections (including meningococcal meningitis), the proportion of patients discontinuing treatment due to AEs, and the proportion of patients forming drug-target-drug complexes (DTDC) after switching from eculizumab or ravulizumab treatment to crovalimab treatment.

COMMODORE 2 is a multicenter, randomized, open-label, active-controlled Phase III clinical trial that evaluated the efficacy and safety of crovalimab (administered subcutaneously once every 4 weeks) compared with eculizumab (administered intravenously once every 2 weeks) in patients with PNH who had not previously received complement inhibitor therapy. The primary endpoints of the study were the proportion of patients not requiring transfusions and the proportion of patients achieving controlled hemolysis (lactate dehydrogenase levels ≤1.5 x ULN).

The results showed that, in the COMMODORE 1 study, patients benefited with low risk after switching from eculizumab or ravulizumab to crovalimab; in the COMMODORE 2 study, crovalimab was non-inferior to eculizumab.

Previously, Roche completed a Phase III study (COMMODORE 3) of Crovalimab for the treatment of Chinese patients with PNH, and based on the results of this study, submitted the product's marketing application in China in August 2022, which was granted priority review (see details: ).

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