AstraZeneca announced in May 2026 that its drug Ultomiris significantly reduced urine protein levels in patients with IgA nephropathy, a chronic kidney disease that pushes thousands of people toward dialysis or transplant each year. The result, from a Phase III trial called I CAN, is the first time the complement-blocking drug has hit a primary endpoint in this condition and could open a new treatment path for patients running out of options.
Ultomiris, known generically as ravulizumab-cwvz, works by shutting down part of the immune system’s complement cascade, a chain reaction of proteins that, in IgA nephropathy, attacks the kidney’s filtering units. The I CAN trial measured the drug’s effect on the 24-hour urine protein-to-creatinine ratio (UPCR) at Week 34. AstraZeneca said the drug met that goal with statistical significance, and that proteinuria reductions appeared as early as Week 10.
What the trial showed and what it didn’t
The Phase III I CAN study, which enrolled an estimated 430 adults with IgA nephropathy, was designed with two co-primary endpoints: the UPCR reduction at Week 34 and a longer-term measure of kidney function called the estimated glomerular filtration rate (eGFR) slope, which tracks how fast the kidneys lose filtering capacity over time. Only the first endpoint has been reported so far.
That distinction matters. Proteinuria, the spillage of protein into urine, is a well-accepted surrogate marker in kidney disease trials. The FDA used it as the basis for accelerated approval of Travere Therapeutics’ Filspari (sparsentan) for IgA nephropathy in 2023. But nephrologists and regulators will ultimately want proof that Ultomiris also slows the actual decline in kidney function. A drug that lowers urine protein without preserving eGFR would face serious questions about real-world benefit.
AstraZeneca has not disclosed the exact magnitude of the proteinuria reduction, the size of the treatment effect versus placebo, or detailed safety data from the trial. A conference abstract published in Nephrology Dialysis Transplantation described the trial’s design but contained no outcome data. Until the full dataset is presented at a medical meeting or published in a peer-reviewed journal, independent researchers cannot judge how clinically meaningful the result is.
Earlier data built the case
The Phase III result did not come out of nowhere. A randomized, double-blind, placebo-controlled Phase 2 trial of ravulizumab in IgA nephropathy, published in the Journal of the American Society of Nephrology, showed proteinuria changes that provided the biological rationale for the larger study. That earlier trial, registered separately as NCT04564339, gave researchers confidence that blocking terminal complement activity could interrupt the immune-driven damage at the root of the disease.
The consistency between the Phase 2 signal and the Phase III primary endpoint strengthens the scientific case. It suggests complement inhibition has a reproducible, measurable effect on the protein leakage that signals ongoing kidney injury in IgA nephropathy.
A crowded and evolving treatment landscape
Ultomiris would not be entering an empty field. IgA nephropathy treatment has shifted rapidly in recent years. Filspari, a dual endothelin and angiotensin receptor antagonist, received accelerated FDA approval in 2023 based on proteinuria data. Novartis is advancing iptacopan (Fabhalta), which targets complement factor B and has received FDA breakthrough therapy designation for IgA nephropathy. Standard care still relies heavily on renin-angiotensin system blockers and blood pressure management, but the pipeline of targeted therapies is deeper than it has ever been.
Ultomiris carries practical hurdles that set it apart from oral competitors. The drug is administered intravenously, which means regular clinic visits. Its U.S. prescribing information, available through DailyMed, includes a boxed warning about serious meningococcal infections, a known risk for any drug that blocks terminal complement. Patients must be vaccinated before starting treatment. For a chronic disease that can unfold over decades, the burden of IV infusions and the long-term infection risk will weigh heavily in treatment decisions.
Cost is another factor. Ultomiris carries an annual price tag exceeding $500,000 for its currently approved indications in rare diseases like paroxysmal nocturnal hemoglobinuria. While pricing for a potential IgA nephropathy indication has not been announced, payers will scrutinize whether the clinical benefit justifies that level of spending, particularly when oral alternatives exist.
What patients and clinicians should watch for
No regulatory filing for Ultomiris in IgA nephropathy has been publicly announced. Full data presentation, regulatory submission, and agency review each take months to years. Patients currently managing the disease with existing therapies are unlikely to see immediate changes in their care based on a top-line press release alone.
The critical questions ahead are specific and answerable, once AstraZeneca releases the full dataset. How large was the proteinuria reduction compared with placebo? Does the eGFR slope show preserved kidney function over time? How did serious adverse events, particularly infections, compare between the treatment and control groups? Were there differences across patient subgroups defined by baseline proteinuria, race, or geography, all of which matter for a disease whose severity varies across populations?
If the complete data show a substantial proteinuria reduction paired with a favorable eGFR trajectory and manageable safety, Ultomiris could become an important option for patients at high risk of progression despite standard care. Those with heavy proteinuria, rapidly declining kidney function, or poor responses to existing treatments would likely be the earliest candidates.
If the proteinuria effect turns out to be modest, if eGFR benefits are marginal, or if serious infections prove more common than expected, the drug’s role could be far narrower than the positive headline suggests. History offers reason for caution: several kidney drugs have looked promising at the surrogate-marker stage and disappointed when longer-term outcomes were measured. The I CAN trial’s Week 34 result is a meaningful step, but the data that will determine whether complement inhibition reshapes IgA nephropathy care have not yet been made public.
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*This article was researched with the help of AI, with human editors creating the final content.
