And IgAN makes five.
With a late Thursday nod from the FDA to reduce protein levels in the urine of patients with primary immunoglobulin A nephropathy (IgAN), AstraZeneca’s Alexion-born Ultomiris has racked up its fifth rare disease indication in the United States.
The green light permits Ultomiris (ravulizumab) to enter into an increasingly competitive market with existing drugs like Callidatas’ Tarpeyo, Travere’s Filspari and Novartis’ Fabhalta, with multiple other pharmas’ competitor candidates waiting in the wings.
Meanwhile, given the accelerated nature of the new approval, AZ remains on the hook to validate whether Ultomiris can also slow kidney function decline in patients with IgAN, a rare inflammatory condition that can lead to chronic and eventually end-stage kidney disease if left unaddressed.
The new label specifically clears Ultomiris to reduce the urine protein symptom known as proteinuria in adults with IgAN at risk of disease progression. Proteinuria is considered a prominent measure of kidney function, and heightened levels are linked with serious kidney disease.
On concrete kidney function preservation, AZ confirmed that its ongoing I CAN study is assessing that metric via change from baseline in patients’ estimated glomerular filtration rate (eGFR) at the 106-week mark, noting that these data are “intended to support traditional FDA approval.”
The approval comes courtesy of results from the phase 3 I Can trial, in which Ultomiris was tied to a 46.6% reduction in 24-hour urine protein creative ratio from baseline at 34 weeks, versus a 5.6% drop seen among those on placebo. This translated to a placebo-adjusted treatment effect of 43.4%, AstraZeneca noted.
The company also highlighted the speed at which proteinuria reduction occurred in Ultomiris patients, at as early as 10 weeks, with those results sustained through the 34-week trial period and largely consistent across various subgroup populations.
While full approval acknowledging the ability to preserve kidney function is the holy grail for an IgAN medicine, the path of adopting an accelerated nod around proteinuria first has been common practice for players in the space.
Ultomiris is also bringing a new mechanism to the IgAN table, with AZ previously suggesting that the drug, as a C5 complement inhibitor, can uniquely block central driver of inflammation in IgAN. Novartis’ Fabhalta is also a complement inhibitor but targets Factor B.
Ultomiris is among the key drugs AstraZeneca inherited by way of its $39 billion Alexion buyout in 2020.
“As the first and only C5 inhibitor approved for the reduction of proteinuria in adults with IgAN, Ultomiris offers a new treatment option for people living with this serious disease,” Marc Dunoyer, CEO of AZ’s Alexion unit, said in a statement, adding that the need for more targeted IgAN treatments is acute since many patients “continue to face the risk of progression to kidney failure.”
Outside the U.S., AZ noted that regulatory reviews of Ultomiris are underway in Japan and beyond.
For all of 2025, the drug generated (PDF) global sales of $4.7 billion, marking a 19% increase at constant currencies over the previous year.