Novartis Seeks Rare Kidney Disease Approvals After Phase III Success

Novartis announced encouraging outcomes from two Phase III trials in rare kidney diseases, presented during the recent European Renal Association Congress. These results pave the way for potential new treatment approvals in this medical field.

The Phase III ALIGN study evaluated the efficacy and safety of Novartis’ investigational drug, atrasentan, an endothelin A (ETA) receptor antagonist, in patients with IgA nephropathy (IgAN). Over a 36-week period, atrasentan significantly reduced proteinuria by 36.1% compared to a placebo. The ALIGN study involved atrasentan alongside supportive care, which includes the highest tolerable dose of a renin-angiotensin system (RAS) inhibitor. Safety assessments showed that atrasentan had a favorable profile, with adverse events consistent with those observed in previous trials.

David Soergel, the global head of Novartis' cardiovascular, renal, and metabolism development unit, highlighted the significance of these findings, noting atrasentan’s potential to revolutionize IgAN management. Novartis is poised to submit a regulatory application for atrasentan to the FDA in the first half of 2024. The ALIGN trial is ongoing and double-blinded, with a final analysis expected in 2026.

Atrasentan, designed for oral administration, is a novel ETA receptor agonist with anti-inflammatory and anti-fibrotic properties. It helps mitigate proteinuria and preserve kidney function in IgAN patients. The drug was initially developed by Chinook Therapeutics, which Novartis acquired in June 2023 for $3.5 billion.

In addition to the ALIGN study results, Novartis revealed findings from the Phase III APPEAR-C3G study. This trial demonstrated that Fabhalta (iptacopan), a factor B blocker, could reduce proteinuria by 35.1% over six months in patients with C3 glomerulopathy (C3G) when combined with supportive care. This reduction was statistically significant compared to a placebo.

Fabhalta also showed a "numerical improvement" in kidney function, evaluated using the estimated glomerular filtration rate over the six-month period. Novartis plans to submit Fabhalta for regulatory approval for C3G in the latter half of 2024. Meanwhile, the APPEAR-C3G study will continue with a six-month double-blind phase, during which all participants will receive the factor B blocker.

Fabhalta, an orally available drug candidate, inhibits factor B, a vital player in the alternative component cascade. Hyperactivation of this pathway in C3G patients results in the accumulation of toxic proteins in kidney glomeruli, causing kidney damage, impaired function, and proteinuria. The FDA initially approved Fabhalta in December 2023 for treating paroxysmal nocturnal hemoglobinuria. Novartis is also exploring Fabhalta’s potential for treating IgAN.

These advancements underscore Novartis' commitment to addressing rare kidney diseases and improving patient outcomes. The company is well-positioned for regulatory success, with both atrasentan and Fabhalta showing significant promise in their respective clinical trials. The continued development and potential approvals of these treatments could mark a significant breakthrough in managing rare kidney conditions, offering new hope to patients worldwide.

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