Ultomiris Effective in Pediatric aHUS Previously Treated With Soliris, Study Suggests

Ultomiris (ravulizumab) is safe and results in stable kidney and blood measurements in children and adolescents with atypical hemolytic uremic syndrome (aHUS) who were previously receiving more frequent infusions of Soliris (eculizumab), a new study indicates.

The findings also suggest that pediatric patients could be treated less often, without compromising safety or efficacy.

The study, “The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab,” was published in Pediatric Nephrology. It was funded by Alexion Pharmaceuticals, which developed both Soliris and Ultomiris.

aHUS is caused by abnormal activation of the complement system — a group of immune-related proteins in the blood. Soliris is an antibody therapy that blocks complement activation by binding to a protein called C5.

While Soliris has been shown to safely and effectively treat aHUS in clinical trials and other studies, the medication does not remain active in the body for very long, necessitating infusions every two weeks, which can be a burden to patients.

Ultomiris is effectively a version of Soliris that works the same way, but has been modified such that it can stay active in the body for longer, so infusions need to be given less frequently. Both Soliris and Ultomiris have been approved to treat children and adults with aHUS in the U.S. and the European Union.

Previous findings from a Phase 3 trial (NCT02949128) demonstrated the efficacy of Ultomiris in adults with aHUS who had never been treated with Soliris.

The new findings stem from a different ongoing Phase 3 clinical trial (NCT03131219), which is evaluating Ultomiris in aHUS patients younger than 18. The researchers — from Alexion and from Japan, Belgium, Spain, and the U.S. — specifically reported findings for the 10 trial participants who had previously been treated with Soliris.

Participants in the trial were given an initial loading dose of Ultomiris, followed by maintenance doses two weeks later, then every 4–8 weeks thereafter. Exact dosages and schedules were individualized based on body weight.

Nine of the 10 participants were male, and the overall median age was 12.5 years. Half of the participants were white, four were Asian, and one was Black.

All completed the initial 26-week study, then enrolled in an extension period. For the data used in this study, the median time on treatment was 50.3 weeks, at which point none of the patients had discontinued treatment.

Kidney disease is a common problem in people with aHUS, since aHUS can cause damage to blood vessels in the kidneys. Results from the trial suggested that Ultomiris maintained kidney function in the 10 participants. None of the them required dialysis prior to the trial, or at any point during the trial.

Additionally, estimated glomerular filtration rate (eGFR) — a measurement of kidney function — remained stable throughout the study. Prior to the start of the trial, median eGFR was 99.8 mL/min/1.73 m². After 26 weeks, it was 93.5 mL/min/1.73 m², and after 50 weeks, it was 104 mL/min/1.73 m².

After one year of treatment, the participants’ stage of kidney disease did not change, which is indicative of stable kidney function.

Various blood measurements, including platelet count, cholesterol, and hemoglobin (the protein that carries oxygen in red blood cells) were also consistent throughout the trial, as was patient-reported fatigue.

All participants reported at least one adverse event, which were mild or moderate in severity in all but one. One participant experienced several serious adverse events related to respiratory infections (e.g., pneumonia), but none of these events were deemed related to the treatment.

The most common treatment-emergent adverse events were upper respiratory infection, reported in four participants, and pain in the back of the mouth, reported in three. All other adverse events were reported in two or fewer participants.

“There were no unexpected safety findings or new safety signals identified,” the researchers wrote. While they acknowledged the difficulty in making accurate comparisons across different clinical trials, they noted that the safety profile for Ultomiris in this trial was generally similar to that of Soliris.

“Based on the available data from this study, patients who switch [from Soliris to Ultomiris] can expect a similar efficacy and safety profile to [Soliris],” the researchers concluded.

Switching to Ultomiris could result in cost savings and improvement to patients’ quality of life, since it requires less frequent infusions, the researchers suggested.

“The results obtained in this study indicate that it is possible for pediatric patients with aHUS to receive treatment less frequently with a dosing interval up to 8 weeks without compromising efficacy and safety,” they wrote.