Ultomiris (ravulizumab)

A long-acting complement blocker with positive Phase 3 results in IgA nephropathy. Already approved for other rare diseases, ravulizumab met its primary proteinuria endpoint in the I CAN trial (April 2026). The FDA accepted AstraZeneca's application and granted it priority review in June 2026, with a decision expected in the fourth quarter of 2026. It is not yet approved for IgA nephropathy.

Ravulizumab blocks complement C5, a protein in the immune cascade that causes inflammation and tissue damage. In IgA nephropathy, complement activation amplifies kidney injury from IgA deposits. By blocking C5, ravulizumab aims to stop this destructive chain reaction and protect kidney function.

Ravulizumab is already approved for other conditions, so its safety profile is well-characterized. Ultomiris carries a boxed warning for serious meningococcal infections, which can become life-threatening or fatal if not caught early. Meningococcal vaccines must be completed or updated at least 2 weeks before the first dose unless delaying treatment is riskier, and the risk stays raised even after vaccination. It is available only through a restricted program called the ULTOMIRIS and SOLIRIS REMS. In the I CAN trial, the most common side effects were upper respiratory infections (11.3% vs 10.2% on placebo), common cold symptoms (9.2% vs 9.0%) and infusion reactions (8.4%).

Given as an intravenous infusion. On its current label for other conditions, adults get a single loading dose, then maintenance infusions 2 weeks later and every 8 weeks after that, with doses based on body weight. The FDA has not yet approved a dose for IgA nephropathy.

Not yet. Ravulizumab is under FDA review for IgA Nephropathy; AstraZeneca (Alexion) has filed an application and a decision is expected in Q4 2026. The FDA calendar page tracks the outcome.

Yes. Ravulizumab (Ultomiris) is already FDA-approved for paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder (NMOSD). The I CAN Phase 3 trial for IgA nephropathy met its proteinuria endpoint in April 2026. The FDA granted that application priority review in June 2026 and is expected to decide in the fourth quarter of 2026, so IgA nephropathy is not yet an approved use.

In the Phase 2 SANCTUARY trial (66 patients), proteinuria fell 41.9% with ravulizumab versus 16.8% with placebo at week 26, a 30.1% treatment effect, suggesting that blocking complement C5 can lower protein in the urine, a marker of kidney damage, in IgA nephropathy.

I CAN is a double-blind, randomized, placebo-controlled Phase 3 trial in 28 countries that enrolled 584 adults with IgA nephropathy, according to ClinicalTrials.gov. In April 2026, AstraZeneca announced it met its first primary endpoint, a drop in proteinuria at week 34. Full results presented in June 2026 showed a 43.4% greater reduction with ravulizumab than with placebo. A second primary endpoint measuring kidney function (eGFR) will be assessed at week 106.

Ravulizumab is given as an intravenous infusion. On its current label for other conditions, adults get a single loading dose, then maintenance infusions 2 weeks later and every 8 weeks after that, with doses based on body weight. The FDA has not yet approved a dose for IgA nephropathy.

Yes. As with all complement C5 inhibitors, meningococcal vaccination is required before starting ravulizumab due to the increased susceptibility to meningococcal infections when complement is blocked.

Ravulizumab blocks complement C5 (terminal pathway), while iptacopan blocks factor B (alternative pathway) and sefaxersen lowers factor B by blocking the messenger RNA the liver uses to make it. Each targets a different point in the complement cascade.