Novartis Triumphs in Phase III for IgAN Treatment, Sets Sights on Regulatory Journey for Complement Inhibitor

Novartis has shared exciting news regarding its investigational complement inhibitor, iptacopan, in the Phase III APPLAUSE-IgAN study. While specific data details were not provided, Novartis announced that iptacopan achieved its pre-specified interim analysis primary endpoint, marking a significant milestone.

In this study, which focuses on patients with IgA nephropathy (IgAN), iptacopan demonstrated a statistically significant and clinically meaningful reduction in proteinuria compared to the placebo group after nine months of treatment. Moreover, the safety profile of iptacopan remained consistent with previous reports.

Encouraged by these positive results, Novartis is now setting its sights on an FDA application for accelerated approval in 2024.

Shreeram Aradhye, Novartis’ Chief Medical Officer and President of Development, expressed optimism about iptacopan’s potential to provide meaningful benefits to IgAN patients.

The APPLAUSE-IgAN study is a randomized, double-blinded, parallel-group, and placebo-controlled trial involving approximately 470 patients with primary IgAN. Patients received iptacopan at a 200-mg oral dose twice daily in addition to supportive care, which included maximally tolerated angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

In addition to proteinuria reduction, the study’s second primary endpoint is the annualized total estimated glomerular filtration rate (eGFR) slope over 24 months. The trial will remain double-blinded to evaluate this endpoint, and the topline data is expected in 2025.

IgAN is a rare and progressive kidney disease triggered by an autoimmune reaction against an abnormal form of the IgA antibody. This reaction results in the accumulation of immune complexes in the kidney, leading to inflammation and damage to the organ, ultimately affecting its function. IgAN primarily affects young adults and is characterized by symptoms such as edema, back pain, and foamy or bloody urine.

Iptacopan is an orally available inhibitor of the alternative complement pathway, a known driver of IgAN.

Novartis’ Phase III success comes after a recent setback for Travere Therapeutics, which disclosed that its kidney drug, Filspari (sparsentan), narrowly missed one of its key endpoints in the Phase III PROTECT study.

Although it failed to show superiority over irbesartan in terms of eGFR total slope improvement, it did achieve statistical superiority for eGFR chronic slope after three months. Filspari had received accelerated approval in February 2023 and is now undergoing the confirmatory study, with a supplemental New Drug Application planned for the first half of 2024 to seek full approval.

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