Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH): Pooled Results from COMMODORE Phase 3 Studies

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and potentially fatal disease characterized by premature destruction of red blood cells due to dysregulated activation of the complement system. Eculizumab, a complement inhibitor, has revolutionized the treatment of PNH by reducing hemolysis and improving patient survival. However, the need for frequent infusions and the risk of adverse events highlight the importance of developing alternative therapies with greater convenience and safety. Crovalimab, a new complement inhibitor with a mechanism of action similar to eculizumab, but with subcutaneous administration and prolonged interval between doses, appears as a promising option. This study aims to compare the safety of crovalimab with that of eculizumab in patients with PNH, using pooled data from the phase 3 COMMODORE studies. The objectives include evaluating the incidence of adverse events, clinical efficacy, and tolerability of crovalimab relative to standard of care. Data were obtained from the combined analysis of two phase 3 studies, COMMODORE 1 and COMMODORE 2, which included patients with PNH treated with crovalimab or eculizumab. The primary outcome was the incidence of serious adverse events (SAEs) and adverse events of special interest (AEEs), such as infections and complement-related reactions. Patients were followed for up to 24 weeks, with regular safety and efficacy assessments, including hematological parameters and hemolysis markers. Statistical analyses compared the groups in terms of safety and clinical efficacy. The results demonstrated that crovalimab had a comparable safety profile to eculizumab, with similar rates of SAEs and EAEs. The incidence of infections was slightly lower in the crovalimab group, suggesting a possible additional benefit related to its subcutaneous administration. In addition, crovalimab maintained clinical efficacy, with adequate control of hemolysis and improvement in hematological parameters, with no significant differences in relation to eculizumab. The discussion highlights that crovalimab can offer practical advantages, such as reducing the frequency of administration and the possibility of self-administration, which can improve treatment adherence and quality of life for patients. The comparable safety of eculizumab reinforces its potential as a viable alternative, especially for patients seeking greater convenience. However, long-term studies are needed to assess the durability of response and safety in larger and more diverse populations. Crovalimab has demonstrated a safety profile comparable to eculizumab, with clinical efficacy maintained in the treatment of PNH. These results support its adoption as an innovative therapeutic alternative, with the potential to improve the convenience and quality of life of patients. Future research should focus on the long-term evaluation and expansion of access to this therapy, consolidating its role in the management of PNH.