– Acceptance based on the Phase III COMMODORE 2 study, which demonstrated crovalimab achieved disease control and was well-tolerated in people with paroxysmal nocturnal hemoglobinuria (PNH) –

– If approved, crovalimab will be the first monthly subcutaneous treatment for PNH, with the option to self-administer outside of a supervised healthcare setting –

– Filing applications have also been accepted in the EU, China and Japan, and submissions to other regulatory authorities around the world are ongoing –

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) for crovalimab, an investigational, novel anti-C5 recycling monoclonal antibody, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). The acceptance was based on results from the pivotal Phase III COMMODORE 2 study, which demonstrated that in people with PNH, crovalimab achieved disease control and was well-tolerated. Results from the Phase III COMMODORE 1 study, demonstrating the consistent benefit-risk profile of crovalimab, also supported the application.

“This filing acceptance reinforces the value of crovalimab, which was engineered to be recycled in the bloodstream with the goal of offering a sustained response while reducing treatment burden,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Crovalimab could provide an option to self-administer as infrequently as every four weeks, thereby reducing clinic visits for people with this lifelong condition.”

PNH is a rare and life-threatening blood condition, which affects approximately 20,000 people worldwide. In PNH, red blood cells are destroyed by the complement system – part of the innate immune system. This causes symptoms such as anemia, fatigue and blood clots, and can lead to kidney disease. C5 inhibitors – treatments that block part of the complement system cascade – have been shown to be effective in treating PNH. Crovalimab is a novel C5 inhibitor that is recycled within the bloodstream, enabling sustained complement inhibition through low-dose, subcutaneous (SC) administration every four weeks.

The BLA was based on results from the Phase III COMMODORE 2 study in people with PNH who have not been previously treated with complement inhibitors. Results from the study demonstrated that crovalimab, administered as SC injections every four weeks, achieved disease control and was non-inferior with comparable safety to eculizumab, a current standard of care, given intravenously every two weeks. Adverse events (AE) in the study occurred in 78% of participants treated with crovalimab and 80% treated with eculizumab, with the most common AE being an infusion-related reaction. The application also included data from the Phase III COMMODORE 1 study, which supported the favorable benefit-risk profile of crovalimab in people with PNH switching from currently approved C5 inhibitors. Data from the COMMODORE 1 and 2 studies were recently presented at the European Hematology Association 2023 Hybrid Congress.

Global Phase III data from the COMMODORE 1 and 2 studies in PNH have been submitted to other regulatory authorities around the world and submissions are ongoing.

Crovalimab is being investigated in a broad clinical development program, including five ongoing Phase III studies and three earlier phase studies in PNH and other complement mediated diseases.

About Crovalimab

Crovalimab is an investigational, 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 infection. Crovalimab, which was created by Chugai Pharmaceutical Co., Ltd, has been engineered to address certain needs of people living with complement-mediated diseases, including providing patients with a potential self-administration option.

Crovalimab works by binding to C5, blocking the last step of the complement cascade and is also recycled within the bloodstream, enabling rapid and sustained complement inhibition. Crovalimab’s recycling properties also enable low dose subcutaneous (SC) administration every four weeks. In addition, crovalimab binds to a different C5 binding site from current treatments, which has the potential to provide a treatment option for people with specific C5 gene mutations who do not respond to current therapies. It is also being evaluated in atypical hemolytic uremic syndrome, sickle cell disease, and other complement mediated diseases.

About the COMMODORE 1 and 2 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 treated previously 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 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.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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