Crovalimab Offers Effective, Less Burdensome Alternative to Eculizumab for PNH Treatment

For patients with paroxysmal nocturnal hemoglobinuria (PNH), crovalimab (Piasky, crovalimab-akkz) has emerged as an additional treatment option with a similar safety and efficacy profile to eculizumab, according to a recent study published in American Journal of Hematology.¹

Patients with PNH stand at an increased risk for thrombotic, among other, events | image credit: Bipul Kumar - stock.adobe.com

Crovalimab is a novel anti-C5 recycling monoclonal antibody that is self-administered every 4 weeks. Its recent FDA approval for the treatment of patients with PNH—aged 13 and older who weigh 40 kg or more²—added an additional treatment option alongside eculizumab and ravulizumab. Eculizumab and ravulizumab are terminal complement inhibitors that also act on C5; both have shown to be tolerable for patients and aid in reducing hemolysis, risk of thrombosis, and demonstrate improved survival rates.¹

“However, the need for frequent IV (intravenous) infusions with eculizumab (every 2 weeks) can interfere with work, education, travels, daily schedules and impact patients' quality of life,” the authors wrote. “Although the introduction of ravulizumab, a C5 inhibitor with an extended half-life versus eculizumab, addressed some of these gaps, there remains a need for additional therapeutic options to reduce treatment burden and increase patient convenience in the context of this lifelong disease.”

Because crovalimab can be self-administered, it presents an opportunity to drastically alter the treatment burden of patients with PNH. The phase 3 COMMODORE 1 trial (NCT04432584) is a global, multicenter, randomized, open-label study that investigated the effect of crovalimab vs eculizumab in C5 inhibitor-naïve patients.

This investigation enrolled adult patients with PNH across 25 countries, encompassing 70 sites. Participants were randomized 1:1 to have eculizumab or crovalimab for 24 weeks. Following this period, they were given the option to either switch to or continue with crovalimab. Hemolysis control and transfusion avoidance were the primary outcomes of concern in this comparison.

A total of 89 patients were included; 45 were randomized to the crovalimab arm and 44 to eculizumab; however, only 42 patients in the eculizumab arm were evaluated in the safety analysis. At least 1 adverse event (AE) was reported by 34 participants from the crovalimab arm (77%) and 28 from the eculizumab arm (67%). The most prevalent AEs were pyrexia (16% vs 2%, respectively), COVID-19 (14% vs 17%), and reactions related to their infusion (14% vs 0%), such as headaches. The authors noted that no serious infusion-related reaction occurred and that all were deemed either mild or moderate.

Seven individuals who switched from eculizumab to crovalimab experienced transient immune complex reactions such as a rash (n = 5), arthralgia and/or myalgia (n = 5), or nausea and dizziness (n = 1). These reactions were also determined to be mild or moderate.

There were serious AEs reported in 14% of patients with crovalimab (n = 6) and 2% with eculizumab (n = 1), but none led to study withdrawal. Furthermore, 41% (n = 18) of patients treated with crovalimab experienced infections compared with 36% (n = 15) of those treated with eculizumab; however, all infections—including more serious ones—were not reported as related to either treatment.

For the evaluation of efficacy, 39 and 37 participants were included in the crovalimab and eculizumab groups, respectively. From baseline through week 25, an average of nearly 93% of patients treated with crovalimab achieved hemolysis control (95% CI, 86.6%-96.4%) vs almost 94% with eculizumab (95% CI, 87.3%-97%).

Participants were able to avoid the need for transfusions at rates of 79.5% (n = 31) and 78.4% (n = 29) with crovalimab and eculizumab.

“With comparable safety and efficacy versus eculizumab in patients with PNH, crovalimab is a new C5 inhibitor treatment option that is potentially less burdensome than existing therapies in the context of this chronic lifelong disease,” the authors concluded.

References

1. Scheinberg P, Clé DV, Kim JS, et al. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024. doi:10.1002/ajh.27413

2. Ryan C. FDA Approves crovalimab for paroxysmal nocturnal hemoglobinuria. OncLive®. June 24, 2024. https://www.onclive.com/view/fda-approves-crovalimab-for-paroxysmal-nocturnal-hemoglobinuria