2-y crovalimab paroxysmal nocturnal haemoglobinuria (PNH) data for fatigue, a relevant symptom in atypical haemolytic uraemic syndrome (aHUS) and PNH

aHUS is a rare, life-threatening, complement-mediated disease characterized by thrombotic microangiopathies. Established C5 inhibitors (C5is), eculizumab and ravulizumab, are effective but burdensome treatments, requiring intravenous infusions every 2 or 8 weeks, respectively. Crovalimab is a novel, low-volume, subcutaneous, self-administrable C5i dosed every 4 weeks. Crovalimab is being evaluated in aHUS in two ongoing global, Phase III, single-arm trials: COMMUTE-a (NCT04861259) and COMMUTE-p (NCT04958265). It was also evaluated in patients (pts) with PNH, another complement-mediated rare blood disorder, in the global, randomised, Phase III COMMODORE 2 (NCT04434092) and COMMODORE 1 (NCT04432584) trials (Röth AJH 2024; Scheinberg AJH 2024). Fatigue is a debilitating symptom in aHUS and PNH; it is among the three most reported symptoms in aHUS (Greenbaum Kidney Int Rep 2020) and the most common symptom in PNH (Cella J Patient Rep Outcomes 2023). Here, we report Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (Smith PM R 2010) data, a widely used pt-reported outcome (PRO) measure in aHUS and PNH, with a median 2-year follow-up from COMMODORE 2 and 1.

COMMODORE 2 enrolled C5i-naive pts, and COMMODORE 1 enrolled C5i-experienced pts with PNH. Pts were randomized 2:1 (COMMODORE 2) and 1:1 (COMMODORE 1) to receive crovalimab (Arm A) or eculizumab (Arm B) for the primary treatment period (baseline to Week 25). After Week 25, pts in Arm A continued crovalimab, while pts in Arm B could switch to crovalimab (Arm B switch). Fatigue was assessed at scheduled visits from baseline until Week 97 using FACIT-Fatigue, a 13-item PRO instrument for fatigue-related symptoms and impacts on daily functioning, with a positively-oriented score from 0 to 52. A ≥5-point increase in score signifies a clinically meaningful improvement (Cella J Patient Rep Outcomes 2023), with the normative population mean score ranging from 43.5–46.6 (Cella J Pain Symptom Manag 2002; Butt J Pain Symptom Manag 2010; Montan Value Health 2018). Mean FACIT-Fatigue scores are reported. The clinical cutoff date (CCOD) was March 12, 2024.

In COMMODORE 2, 129 of 135 pts in Arm A continued crovalimab treatment, and 68 of 69 pts in Arm B switched to crovalimab in the extension period. At Week 25, Arm A pts' fatigue levels were similar to those without PNH. Mean absolute FACIT-Fatigue scores were maintained from >Week 25 to Week 97, ranging from 41.9–44.3 (Arm A) and 40.3–42.2 (Arm B switch) (Figure 1). In COMMODORE 1, all 44 pts in Arm A continued crovalimab, and 40 of 42 in Arm B switched to crovalimab. Mean scores remained stable from >Week 25 to Week 97, ranging from 40.8–42.9 (Arm A) and 38.2–40.8 (Arm B switch) (Figure 2). At the CCOD, 116 pts (Arm A) and 59 pts (Arm B switch) in COMMODORE 2, and 42 pts (Arm A) and 32 pts (Arm B switch) in COMMODORE 1 continued crovalimab treatment.

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The improvements in pt-reported fatigue levels observed with crovalimab in COMMODORE 2 were maintained over a median 2-year follow-up. Similarly, fatigue levels remained stable over the same period in COMMODORE 1. These results support crovalimab’s long-term benefits. The ongoing COMMUTE-a and COMMUTE-p trials evaluating crovalimab in aHUS continue to assess fatigue with the FACIT-Fatigue PRO measure, given its importance in this population.

This abstract was previously submitted to European Society for Paediatric Nephrology 2024.