Novartis said its pill for rare kidney disease led to significantly lower protein levels among patients in a late-stage trial, setting up a potential regulatory filing next year.

The Phase 3 study of iptacopan (LNP023) in IgA nephropathy (IgAN) met its pre-specified, nine-month primary endpoint, demonstrating a “clinically meaningful and highly statistically significant” effect versus placebo in reducing the spilling of protein into the urine, or proteinuria, Novartis said. 

The announcement came Monday as part of a pre-planned update of the study, dubbed APPLAUSE-IgAN. 

Although topline results on itacopan’s ability to slow IgAN progression – the trial’s other primary endpoint – aren’t expected for another two years, the Swiss drugmaker plans to submit for accelerated approval in 2024 after reviewing results with the Food and Drug Administration.

The positive results reinforce the potential of iptacopan to provide “clinically meaningful benefit to patients with IgAN, a debilitating disease that affects mostly young adults,” stated Dr. Shreeram Aradhye, president of development and chief medical officer at Novartis.

Each year about 25 people per million worldwide are diagnosed with IgAN, a complement-mediated kidney disease and a major cause of chronic kidney disease and kidney failure. Up to 30% of those who have IgAN with persistent higher levels of proteinuria may progress to kidney failure within 10 years.

Given this context, there is a need for more disease-slowing IgAN treatments. 

Last month, rival company Travere Therapeutics’ Filspari (sparsentan) narrowly missed statistical significance in a trial designed to confirm its effect on disease progression.

Iptacopan aims to address IgAN and other complement-mediated diseases by inhibiting factor B, a protease essential to the alternative complement pathway.

While Novartis’ press release contained no quantitative data, a Phase 2 IgAN study of iptacopan (200mg twice daily) demonstrated a 23% reduction in proteinuria as compared to placebo at 90 days and proteinuria continued to decrease after this period. 

As its primary endpoint at study end, APPLAUSE-IgAN is relying on a surrogate measure of progression in kidney disease known as glomerular filtration rate (eGFR) slope. The study will continue in double-blind fashion to evaluate that ability, with topline results expected in 2025. Thus far, the safety profile of iptacopan (200 mg twice daily) has been consistent with previously reported data. 

The interim readout marks the third positive Phase III trial for iptacopan, as Novartis tests the drug in several other indications. 

Regulators look set to approve the drug in paroxysmal nocturnal hemoglobinuria (PNH) later this year. Analysts from Credit Suisse forecast sales of $600 million in PNH and $3.2 billion, including all indications, by 2030.

Meanwhile, Travere’s Filspari has accelerated approval in the U.S. and the confirmatory trial was intended to support conversion to full approval via a supplemental NDA/sNDA. The ball is now in FDA’s court, though analysts don’t think the agency will remove it from the market. 

That’s because the benefit demonstrated by Filspari on its eGFR slope endpoint is still above the range generally thought to be clinically meaningful. That said, September’s miss was “very disappointing and introduces some regulatory risk,” Leerink’s Joseph Schwartz warned investors at the time.