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The FDA the complement C5 inhibitor crovalimab (Piasky) for treating paroxysmal nocturnal hemoglobinuria (PNH), a rare but life-threatening blood disease.

Indicated for PNH in adults and children 13 years and up with a body weight of at least 40 kg (~88 lb), the anti-C5 monoclonal antibody was engineered to be recycled in the bloodstream to sustain responses and reduce patients' treatment burden, . After a series of loading doses, maintenance doses can be administered by subcutaneous injection every 4 weeks.

PNH is caused by mutations in the PIGA gene, which affects red blood cells (RBCs), and is characterized by anemia due to the destruction of RBCs, fatigue, blood clots, and impaired bone marrow function. People with PNH are typically diagnosed in their mid-30s to early 40s. Median survival is 10 years after a diagnosis, though some survive for decades.

Primary support for the approval of crovalimab came from , a phase III noninferiority study that randomized 204 PNH patients 2:1 to either crovalimab or the C5 inhibitor eculizumab (Soliris), a current standard of care that requires intravenous injection. None of the mostly adult patients in the study had previously received treatment with a C5 inhibitor.

The open-label trial showed crovalimab to be noninferior to eculizumab in achieving disease control, with similar proportions of patients in each arm achieving hemolysis control and transfusion avoidance, the study's coprimary endpoints:

• Hemolysis control: 79.3% vs 79%, respectively
• Transfusion avoidance: 65.7% vs 68.1%

Secondary endpoints also showed a similar degree of benefit between the two agents: breakthrough hemolysis (10.4% with crovalimab vs 14.5% with eculizumab) and hemoglobin stabilization (63.4% vs 60.9%).

Data from three trials, including COMMODORE 2, provided support for the approval in children.

According to the , common adverse events in trials of crovalimab included infusion-related reactions, infections (respiratory tract and viral), and Type III hypersensitivity reactions, which can occur when patients switch between C5 inhibitors.

Labeling for crovalimab also includes a boxed warning over the increased risk of life-threatening infections caused by Neisseria meningitidis. Before initiating a first dose, patients should receive meningococcal vaccination in accordance with Advisory Committee on Immunization Practices recommendations to reduce the risk of these infections.

Crovalimab is contraindicated in patients with an unresolved serious N. meningitidis infection and for those with serious hypersensitivity to the drug or any of its components. Breastfeeding while using crovalimab is not recommended.

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