Already approved to treat four rare diseases, AstraZeneca’s Ultomiris has shown its ability against another rare disorder, IgA nephropathy (IgAN).
In a phase 3 trial of adults who are at risk of progression of the kidney disease, Ultomiris delivered a clinically meaningful and statistically significant reduction in protein from the urine after 34 weeks, AZ said Tuesday. The reductions of proteinuria were evident as early as after 10 weeks of treatment, according to the company.
With the interim result, the study has achieved one of its two primary endpoints. The other primary endpoint—the change from baseline in estimated glomerular filtration rate (eGFR)—will be assessed at week 106.
While advancing the trial toward its completion, AZ said it will seek accelerated approval in the indication and will present trial results at a future medical conference.
The IgAN space has become increasingly crowded with drug offerings from Calliditas Therapeutics, Travere Therapeutics, Novartis and Otsuka, all with their initial accelerated approvals based on proteinuria data.
More than 500 participants in the trial were randomized to receive Ultomiris or placebo, administered intravenously. Patients in the treatment arm received a loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance doses beginning on Day 15 and then every eight weeks through the 106-week blinded period.
IgAN is an inflammatory kidney disorder in which abnormal proteins accumulate in the kidneys, causing inflammation that limits the ability to filter blood. IgAN can lead to chronic kidney disease, ultimately requiring dialysis or a transplant. Of the 560,000 people who are diagnosed with IgAN in the US, EU5 and Japan, 60% are eligible for treatment, AZ said.
As a C5 inhibitor, Ultomiris can block the “terminal complement activation” which is the “central driver of kidney inflammation in IgAN,” Jonathan Barratt, M.D., a professor at the University of Leicester and a trial investigator, said in the release.
With that mechanism, Ultomiris would need to compete directly with Novartis' complement inhibitor Fabhalta, which recently showed it could slow kidney function decline and IgAN progression as measured by change in eGFR.
Ultomiris was one of the key drugs AZ gained in its $39 billion acquisition of Alexion in 2020. By then, the FDA had already approved Ultomiris as a treatment for the blood disorders paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (AHUS).
In the last four years, the FDA has signed off on Ultomiris to treat autoimmune diseases general myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD).
Last year, Ultomiris generated (PDF) worldwide sales of $4.7 billion, which were up by 19% from 2024.