Following the recent Chinook Therapeutics acquisition, the Novartis experimental IgA nephropathy therapeutic atrasentan significantly reduced protein in the urine of patients compared to placebo.
Pictured: Novartis office in Basel, Switzerland/iStock, Michael Derrer Fuchs
Topline data from the Phase III ALIGN study showed that Novartis’ investigational endothelin A receptor antagonist atrasentan met its primary endpoint, significantly reducing protein in the urine of patients with IgA nephropathy, the company announced Monday.
Novartis did not reveal specific data in its announcement but said that patients treated with atrasentan saw a “clinically meaningful and highly statistically significant” decrease in proteinuria compared with placebo. ALIGN also found atrasentan’s safety profile to be consistent with what had been established in previous trials.
With these data, Novartis is gearing up for an FDA submission in 2024 for a potential accelerated approval in the U.S. Novartis CMO Shreeram Aradhye said in a statement that ALIGN’s findings demonstrate “the potential of atrasentan to improve outcomes” in IgA nephropathy (IgAN).
Atrasentan is an orally available selective antagonist of the endothelin A receptor that works by exerting anti-inflammatory and anti-fibrotic effects to counter proteinuria in IgAN, as well as preserve kidney function. Novartis added atrasentan to its portfolio in June 2023, when it bought Chinook Therapeutics for $3.2 billion upfront and up to $300 million in contingent value rights.
ALIGN will continue as a blinded study, evaluating the therapy’s effects on kidney function—as measured by the estimated glomerular filtration rate—over 136 weeks of follow-up. Novartis expects top-line results from this analysis in the first quarter of 2026.
The Chinook acquisition also gave Novartis zigakibart, a second IgAN asset and an investigational antibody that targets the APRIL extracellular protein, which is known to be highly expressed in IgAN and is linked with poor disease prognosis. Zigakibart entered Phase III development in July 2023.
Atrasentan and zigakibart now join Novartis’ own IgAN hopeful iptacopan, an oral inhibitor of the complement pathway, which is a known disease driver when overactivated. Earlier this month, Novartis touted promising top-line data from its Phase III APPLAUSE-IgAN study, showing that iptacopan met its pre-specified primary endpoint.
As in the case of atrasentan, iptacopan treatment significantly reduced proteinuria in IgAN patients. Novartis is likewise building up to an FDA application for iptacopan, eyeing potential accelerated approval in 2024.
Elsewhere in the IgAN space, Seattle-based Omeros announced two weeks ago that it was dropping plans to win an FDA approval for its candidate narsoplimab following an interim Phase III analysis, which found that the investigational IgAN therapy did not significantly outperform placebo at reducing proteinuria.
A month earlier, in September 2023, Travere’s Filspari (sparsentan) missed one of its key endpoints in a confirmatory study.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
