The FDA clears Ultomiris for IgA nephropathy under accelerated approval

The Food and Drug Administration has approved ravulizumab-cwvz, sold as Ultomiris, to reduce protein leakage in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk of their kidney disease progressing [s1]. Recorded against supplement S-046 of the drug's licence on 21 October 2026, it is the fifth indication for a complement inhibitor first cleared in 2018 for a pair of rare blood disorders [s1][s2].

What makes the decision worth reading closely is the basis on which it was granted. The label states plainly that the indication "is approved under accelerated approval based on reduction of proteinuria," and that it "has not been established whether ULTOMIRIS slows kidney function decline in patients with IgAN" [s1]. Continued approval, the agency adds, may be contingent on verification of clinical benefit in a confirmatory trial [s1]. The drug cleared the bar on a surrogate marker, not on the outcome patients and their nephrologists ultimately care about.

What IgA nephropathy is

IgA nephropathy is the most common primary glomerular disease worldwide. Deposits of immunoglobulin A build up in the kidney's filtering units, the glomeruli, provoking inflammation that lets protein leak into the urine. Heavy, sustained proteinuria is both a sign of damage and a driver of it: the more protein spills through, the faster kidney function tends to decline, and a sizeable share of patients progress to kidney failure over their lifetime. Standard care controls blood pressure and blocks the renin-angiotensin system, and more recently adds SGLT2 inhibitors — but many patients keep leaking protein despite it.

Ravulizumab attacks a different target. It is a long-acting inhibitor of the complement cascade, part of the innate immune system, and the thinking is that damping complement activity blunts the inflammatory injury driving the disease.

The evidence behind the approval

The efficacy data come from a single trial, ALXN1210-IgAN-320 (NCT06291376), a randomised, double-blind, placebo-controlled study in adults with biopsy-proven IgAN who were still leaking protein on a maximally tolerated RAAS inhibitor [s1]. The approval rests on a pre-planned interim analysis of the first 352 patients in the main cohort who could reach the week 34 visit — 176 assigned ravulizumab and 176 placebo, out of 485 enrolled [s1].

The primary endpoint was the percent reduction in urine protein-to-creatinine ratio (UPCR) at week 34 [s1]. Protein fell by a geometric mean of 47% on ravulizumab against 6% on placebo, a placebo-adjusted reduction of 43% (95% CI 34 to 52, p < 0.0001) [s1]. That is a clear separation on the surrogate the approval was built on.

What the surrogate does and does not show

Proteinuria is an accepted stand-in because lowering it has, across several drug classes, tracked with slower kidney decline. But it is still a stand-in. The label's own language is the honest framing: the trial measured protein, not preserved kidney function, and whether the drug keeps kidneys working longer is a question the confirmatory phase of the same study is designed to answer [s1]. Readers should hold the 43% figure as a protein result, not a proof that fewer patients will reach dialysis.

How it is given, and its risks

Ravulizumab is an intravenous infusion, dosed by body weight with maintenance every eight weeks [s1]. Its central safety problem is unchanged across every indication: by blocking complement it strips away a defence against Neisseria meningitidis, and the label carries a boxed warning for serious and potentially fatal meningococcal infection [s1]. Patients must be vaccinated at least two weeks before the first dose, and the drug is available only through a restricted REMS programme shared with its sister drug Soliris [s1]. The most common adverse reaction reported in the IgAN group was upper respiratory tract infection [s1].

What to watch

Two things. First, the confirmatory read-out: accelerated approval is provisional, and the indication's future turns on whether longer follow-up shows preserved kidney function, not just less protein [s1]. Second, where ravulizumab sits among a suddenly crowded field of IgAN drugs — it now competes with other complement-targeted and endothelin-targeted agents, and clinicians will be weighing an eight-weekly infusion with a meningococcal boxed warning against that lineup [s1].

Red flags: anyone treated with a complement inhibitor who develops fever, headache with a stiff neck, confusion or a rash should seek emergency care, as these can signal meningococcal infection. This article describes an FDA regulatory action and is not medical advice. Decisions about IgA nephropathy treatment are for patients and their treating nephrologists.