FDA approves first C5 inhibitor to reduce protein in urine for IgAN
Ultomiris wins accelerated approval based on Phase 3 trial results
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The FDA has granted accelerated approval to Ultomiris to reduce protein in the urine of adults with primary IgA nephropathy (IgAN) at risk of disease progression. (Image from iStock)
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ultomiris (ravulizumab) to reduce protein in the urine of adults with primary immunoglobulin A nephropathy (IgAN) who are at risk of disease progression.
Accelerated approval allows a therapy to be marketed based on early clinical trial results suggesting it is likely to benefit patients. In this case, the FDA based its decision on evidence that Ultomiris reduces proteinuria, or excess protein in the urine, a sign of kidney damage. However, it has not yet been established whether Ultomiris slows kidney function decline in people with IgAN. Continued approval may depend on additional results from the ongoing clinical trial confirming the treatment’s benefit.
According to AstraZeneca, which markets Ultomiris through its subsidiary Alexion, AstraZeneca Rare Disease, Ultomiris is the first and only C5 inhibitor approved by the FDA for IgAN. This class of medications blocks a protein involved in the immune system called C5. IgAN is estimated to affect more than 200,000 people in the U.S.
“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 Alexion, said in a company press release. “Many patients continue to face the risk of progression to kidney failure, underscoring the need for more targeted therapies that can slow the course of disease.”
FDA approval follows priority review of Ultomiris
Ultomiris’ approval comes about four months after the FDA granted its application priority review. This gives the agency a goal of reviewing the application within six months, compared with 10 months under standard review. Similar applications are under review by regulatory agencies in Japan and other countries.
IgAN is a rare kidney disorder in which abnormal IgA antibodies form clusters with other antibodies and build up in the kidneys. These clusters can activate a group of proteins called the complement system, leading to inflammation and kidney damage. About half of people with IgAN who have high levels of protein in their urine or reduced kidney function are at high risk of developing kidney failure within 10 years of diagnosis.
Ultomiris is given through an infusion into a vein and works by blocking part of the immune system called the complement system. It is already approved in the U.S. for other diseases involving this system, including paroxysmal nocturnal hemoglobinuria, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder.
Ultomiris specifically blocks a complement protein called C5 and is the first C5 inhibitor approved for IgAN in the U.S. Another FDA-approved complement inhibitor for IgAN, Fabhalta (iptacopan), blocks a different protein called factor B.
Ultomiris’ accelerated approval for IgAN was based on an early analysis of data from a global Phase 3 clinical trial known as I CAN (NCT06291376). The study is comparing Ultomiris with a placebo in more than 500 adults with IgAN at risk of disease progression. Participants received an initial infusion, followed by another infusion two weeks later and then infusions every eight weeks.
After 34 weeks, or about eight months, Ultomiris significantly reduced proteinuria compared with placebo, with a placebo-adjusted reduction of 43.4%, according to AstraZeneca.
Ultomiris safety findings consistent with known profile
According to AstraZeneca, safety findings from the I CAN trial were consistent with Ultomiris’ known safety profile. The most common adverse events reported among patients receiving Ultomiris were upper respiratory tract infection, nasopharyngitis (the common cold), and infusion-related reactions.
“For many people living with IgAN, persistent proteinuria remains a significant challenge despite available treatments, signalling ongoing kidney injury and heightened risk of disease progression,” said Richard Lafayette, MD, external scientific committee co-chair of the I CAN trial at Stanford University Medical Center. “With this approval of Ultomiris, physicians now have a C5 inhibitor that delivers sustained … complement inhibition, targeting a central driver of kidney inflammation to meaningfully reduce proteinuria in patients living with this progressive disease.”
The I CAN study is still ongoing to determine whether Ultomiris slows the decline in kidney function compared with placebo over about two years. Researchers will measure changes in estimated glomerular filtration rate (eGFR), which estimates how well the kidneys filter blood.
AstraZeneca says the final trial results are intended to support traditional FDA approval of Ultomiris for IgAN.
The FDA’s decision to give Ultomiris accelerated approval “reflects the importance of continued innovation to help improve outcomes for people living with IgAN,” said Bonnie Schneider, director and co-founder of the IgA Nephropathy Foundation. “With its approved use across several other rare diseases and established safety profile, Ultomiris provides a new treatment option in IgAN that gives patients – and their physicians – more choice as they navigate their care.”
