On crovalimab, 59.5 percent of treatment-naive aHUS participants had a complete TMA response

In the Phase III COMMUTE-a study of crovalimab in atypical hemolytic uremic syndrome (aHUS), 59.5 percent of 37 analyzed participants in the naive cohort had a complete thrombotic microangiopathy response (cTMAr) from baseline to Week 25 (95% confidence interval 43.49 to 73.65), the ClinicalTrials.gov record shows. Hoffmann-La Roche is the sponsor, and the record now holds posted results for 83 enrolled adults and adolescents. Sites running aHUS studies and the doctors at them have single-arm data for both treatment-naive and switch participants, with dialysis counts at Week 25.

Why it matters

The record's brief summary says the study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS. The label for PIASKY (crovalimab), version published Dec 02, 2025, lists treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg. That label version does not list aHUS under Indications and Usage. The study record sets a minimum age of 12 Years.

Primary outcome and dialysis numbers

The record lists results first posted on October 30, 2026.

Primary outcome, naive cohort: 59.5 percent of 37 participants had a cTMAr anytime from baseline to Week 25 (after 24 weeks on treatment), 95% confidence interval 43.49 to 73.65.
The record defines cTMAr as all of the following at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: platelet count at or above the lower limit of normal; lactate dehydrogenase at or below the upper limit of normal; and a decrease of at least 25% in serum creatinine from baseline. Participants with normalized creatinine at baseline were excluded from the analysis, and the percentage was rounded off.
Dialysis at baseline, naive cohort: 53.1 percent of 32 participants (95% confidence interval 36.45 to 69.13).
Dialysis at Week 25, naive cohort: 3.1 percent (95% confidence interval 0.55 to 15.74).
Dialysis, switch cohort: 0 percent of 39 participants at baseline and at Week 25 (95% confidence interval 0.00 to 8.97).

On change in dialysis status, the record lists for the naive cohort 12.5 percent who initiated dialysis at any timepoint, 53.1 percent who discontinued dialysis, 0 percent who remained on dialysis and 34.4 percent who remained dialysis-free throughout. All 39 analyzed participants in the switch cohort, 100 percent, remained dialysis-free throughout.

Study design and participants

COMMUTE-a is a Phase III, multicenter, single-arm study with a single group. It began on October 22, 2021, and reached primary completion on October 9, 2025. The record lists an estimated study completion date of August 20, 2029, and the overall status as active, not recruiting.

The record states that 83 participants were enrolled at 42 investigative sites across 16 countries, in cohorts based on prior exposure to complement inhibitor therapy:

Naive cohort: participants with no prior complement inhibitor therapy.
Switch cohort: participants who switched to crovalimab from eculizumab or ravulizumab.
C5 SNP cohort: participants with a documented C5 polymorphism.

In the 24-week primary treatment period, 41 participants started in the naive cohort, 41 in the switch cohort and 1 in the C5 SNP cohort. Of those, 34, 39 and 0 completed. The efficacy-evaluable population was 37 in the naive cohort and 41 in the switch cohort.

The dose depended on body weight. Participants weighing 40 kg or more and under 100 kg received 1000 mg intravenously on Week 1 Day 1, and participants weighing 100 kg or more received 1500 mg. Both groups then received 340 mg subcutaneously on Week 1 Day 2 and on Weeks 2, 3 and 4. Maintenance doses followed every 4 weeks starting at Week 5, at 680 mg or 1020 mg by weight, for a total of 24 weeks of primary treatment.

Safety measures

The adverse events table lists, by cohort, the number of participants affected out of those at risk:

Naive cohort: 3 of 41 in the deaths table, 14 of 41 with serious adverse events and 33 of 41 with other adverse events.
Switch cohort: 0 of 41 in the deaths table, 10 of 41 with serious adverse events and 39 of 41 with other adverse events.
C5 SNP cohort: 0 of 1 in the deaths table, 1 of 1 with serious adverse events and 1 of 1 with other adverse events.

What remains uncertain

The record marks the reporting status of the measure "All Cohorts: Change From Baseline in Total C5 Concentrations in Crovalimab-treated Participants" as not posted. It lists an estimated study completion date of August 20, 2029, and the safety tables report data collected up to the primary completion cut-off.