AZ grabs FDA nod for Ultomiris in rare kidney disease IgAN

AstraZeneca has staked a claim to the increasingly crowded IgA nephropathy (IgAN) market with an accelerated approval from the FDA for Ultomiris, becoming the drug's fifth disease indication.

Ultomiris (ravulizumab) is the first complement C5 inhibitor to be approved in the US for IgAN, a rare disorder that occurs when antibodies accumulate in the kidneys, causing inflammation and scarring and potentially leading to chronic kidney disease (CKD).

AZ's drug has been approved to reduce proteinuria – a marker for kidney function and a surrogate marker for disease activity in IgAN – in patients who are at risk of progression.

IgAN is the most common primary glomerulonephritis globally, with between 25 and 50 cases per million people a year, and is estimated to affect more than 200,000 people in the US.

Ultomiris' latest approval is supported by the phase 3 I CAN trial, which showed that an infusion with the C5 inhibitor every eight weeks, after a loading dose, led to a 43.4% reduction in proteinuria compared to placebo at 34 weeks.

The accelerated approval means that AZ will have to provide additional data from I CAN to show that the improvement in proteinuria with Ultomiris translates into a slowdown in kidney function decline. To that end, the study is charting estimated glomerular filtration rate (eGFR) over 106 weeks and, if results are positive, should support full FDA approval for IgAN.

Bonnie Schneider, director and co-founder of the IgAN Foundation, welcomed the approval, saying that it "reflects the importance of continued innovation to help improve outcomes for people living with IgAN."

She added: "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."

Regulatory submissions based on the interim results from the I CAN trial are also under review in Japan and other countries, said AZ.

The IgAN market is experiencing an unprecedented surge in new drug approvals, with half a dozen new therapies reaching the US market in the last decade and even more coming through the industry pipeline.

Ultomiris is already approved to treat paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome (HUS), generalised myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD), and is one of AZ's top-selling products, bringing in revenues of $2.58 billion in the first six months of the year.

The company is also testing the drug in haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), with regulatory filings in progress.