With back-to-back victories in IgA nephropathy and C3 glomerulopathy, Novartis on Saturday said it is planning to make regulatory submissions for the rare kidney diseases this year.
Novartis on Saturday posted two promising Phase III readouts in rare kidney diseases, setting the pharma up for two potential approvals in the space. The company presented these data at the European Renal Association Congress over the weekend.
Results from the Phase III ALIGN study showed that at 36 weeks, Novartis’ investigational endothelin A (ETA) receptor antagonist atrasentan reduced proteinuria by 36.1% in patients with IgA nephropathy (IgAN), compared with placebo. ALIGN tested atrasentan in combination with supportive care, which consists of the maximally tolerated stable dose of renin-angiotensin system (RAS) inhibitor.
In terms of safety, ALIGN found that atrasentan had a favorable overall profile and its adverse events were consistent with what had previously been reported in other studies.
Novartis said it is “on track” to submit a regulatory application for atrasentan with the FDA in the first half of 2024. ALIGN is an ongoing double-blind, placebo-controlled Phase III trial. Final analysis from the study is expected in 2026.
David Soergel, global head of Novartis’ cardiovascular, renal and metabolism development unit, in a statement said that these results underscore atrasentan’s “potential to help transform how IgAN is managed.”
Designed to be orally available, atrasentan is an investigational ETA receptor agonist with anti-inflammatory and anti-fibrotic effects, countering proteinuria and preserving kidney function in IgAN. Novartis was originally discovered by Chinook Therapeutics, which Novartis acquired in June 2023 for $3.5 billion.
Novartis on Saturday also unveiled data from the Phase III APPEAR-C3G study, demonstrating that its factor B blocker Fabhalta (iptacopan) can reduce proteinuria by 35.1% at six months when used on top of supportive care in patients with C3 glomerulopathy (C3G). This effect was statistically significant versus placebo, with a p-value of 0.0014, according to the company.
Fabhalta also resulted in a “numerical improvement” in kidney function, as assessed by estimated glomerular filtration rate over six months.
The pharma is preparing for regulatory submissions for Fabhalta in C3G in the second half of 2024. In the meantime, APPEAR-C3G will continue with a six-month double-blind phase, where all patients will be treated with the factor B blocker.
Fabhalta is an orally available drug candidate that blocks factor B, which plays a critical role in the alternative component cascade. In C3G, the hyperactivation of this pathway leads to the toxic buildup of proteins in kidney glomeruli, which in turn leads to kidney damage, poor kidney function and protein in the urine.
The FDA first approved Fabhalta in December 2023 for the treatment of paroxysmal nocturnal hemoglobinuria. Novartis is also studying Fabhalta for IgAN.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
