Atypical Haemolytic Uraemic Syndrome (aHUS)

Crovalimab led to high response rates in adolescents and adults with atypical haemolytic uraemic syndrome (aHUS), while being associated with some serious infections, according to data reported by Dr Bradley Dixon (University of Colorado Anschutz, CO, USA) [1].

The COMMUTE-a (NCT04861259) phase 3 trial was the sister study of COMMUTE-p (NCT04958265) and had a similar study design. Briefly, patients were eligible if they were aged ≥12 years and had a body weight ≥40 kg. As in the paediatric study, 2 cohorts were enrolled: a treatment-naïve cohort (no prior complement inhibitor therapy) and a switch cohort. The primary endpoint was the proportion of patients achieving a complete thrombotic microangiopathy response (cTMAr) at any time through week 25, defined as a platelet count ≥ the lower limit of normal, normalisation of lactate dehydrogenase (LDH), and a ≥25% improvement in serum creatinine from baseline. A prespecified efficacy threshold of 40% was set for the primary endpoint. Each cohort included 41 patients.

The trial met its primary endpoint. In the treatment-naïve cohort, 59.5% of patients (95% CI 43.5%–73.7%) achieved cTMAr by week 25, with a median time to response of 12.1 weeks. Among the 17 patients who required dialysis at baseline, all had discontinued dialysis by week 25. In the switch cohort, all 41 patients maintained cTMAr through week 25, and all remained off dialysis. Overall, crovalimab was well tolerated. Serious infections were reported in 14.6% of patients in the treatment-naïve cohort and 17.1% of patients in the switch cohort. Transient immune complex reactions occurred in 9.8% of patients in the switch cohort, and all resolved within 2 weeks.

“The study met its primary endpoint, with 59.5% of treatment-naïve patients achieving cTMAr by the end of the primary analysis period,” concluded Dr Dixon. “All patients in the switch cohort met their efficacy endpoint of maintenance of cTMAr control. Together, these findings support a favourable benefit-risk profile for crovalimab, further reinforced by the results from COMMUTE-p.”

Dixon B, et al. Efficacy, safety and pharmacokinetics/pharmacodynamics of crovalimab for atypical haemolytic uraemic syndrome (aHUS): Phase III COMMUTE-a trial. ERA 2026, 3–6 June. Glasgow, Scotland.

Crovalimab led to high response rates in paediatric patients with atypical haemolytic uraemic syndrome (aHUS), while being associated with some infectious events.

Dr Maria Helena Vaisbich (University of São Paulo, Brazil) presented results from COMMUTE-p (NCT04958265), a phase 3 trial evaluating weight-based dosing of crovalimab in paediatric participants with aHUS [1]. Patients were eligible if they were aged 28 days to <18 years and had a body weight ≥5 kg. Two cohorts were enrolled: a treatment-naïve cohort (no prior complement inhibitor therapy) and a switch cohort (patients switching from eculizumab or ravulizumab). The primary endpoint was the proportion of patients achieving a complete thrombotic microangiopathy response (cTMAr) at any time through week 25, defined as a platelet count ≥ the lower limit of normal, normalisation of lactate dehydrogenase (LDH), and a ≥25% improvement in serum creatinine from baseline. Overall, 21 patients were included in the naïve cohort and 20 in the switch cohort.

In the naïve cohort, 70.6% of patients (95% CI 46.9%–86.7%) achieved cTMAr by week 25, with a median time to response of 8.7 weeks. Furthermore, all 6 patients who required dialysis at baseline had discontinued dialysis by week 25. In the switch cohort, 100% of patients maintained cTMAr through week 25, and none required dialysis. Serious infections were reported in 33.3% of patients in the naïve cohort and 20.0% of patients in the switch cohort. No deaths or transient immune complex reactions were reported.

“COMMUTE-p demonstrated a clinically meaningful cTMAr, and all treatment-naïve patients who required dialysis at baseline were off dialysis by week 25,” concluded Dr Vaisbich. “Patients in the switch cohort maintained cTMAr and also remained off dialysis. The study showed a favourable risk-benefit profile for crovalimab, supporting its use in paediatric patients with aHUS.”

Vaisbich MH, et al. Efficacy, safety and pharmacokinetics/pharmacodynamics of crovalimab for paediatric atypical haemolytic uraemic syndrome: Phase III COMMUTE-p trial. ERA 2026, 3–6 June. Glasgow, Scotland.

COMMUTE-a: Additional positive results with crovalimab in adolescents and adults with aHUS

COMMUTE-p: Positive results with crovalimab in paediatric aHUS