Atrasentan found superior to placebo for proteinuria reduction in the Phase 3 Trial for IgA Nephropathy.

The conditions affect young adults primarily and are the major cause of chronic kidney disease and kidney failure worldwide.

Novartis has announced positive results from the interim analysis of the ongoing Phase III ALIGN study of Atrasentan.

This study met its primary endpoint. The primary efficacy endpoint of this study is to assess the change in protein in the urine, as measured by the urine protein to creatinine ratio (UPCR), from the baseline to 36 weeks. Additionally, the study aims to evaluate the change in kidney function, as measured by estimated Glomerular Filtration Rate (eGFR), from the baseline to 136 weeks and to assess the safety and tolerability of the treatment.

The trial has demonstrated the superiority of Atrasentan compared to placebo in proteinuria reduction at 36-week interim analysis. The safety profile is consistent with previous findings. Atrasentan is an oral endothelin A receptor antagonist (ERA), in IgAN. The trial has reported it to be associated with a clinically meaningful and highly statistically significant reduction in proteinuria (protein in urine) in IgAN patients receiving supportive care. (maximally tolerated and stable dose of a renin-angiotensin system inhibitor).

Key findings of this trial are:

• Three hundred forty patients with biopsy-proven IgAN with baseline total proteinuria over one gram/day despite optimized RAS inhibitor treatment were randomized to receive once-daily oral doses of 0.75 mg atrasentan or placebo for approximately 132 weeks.
• Patients continue receiving a maximally tolerated and stable dose of an RAS inhibitor as supportive care.
• An additional group of 64 patients receiving a stable dose of SGLT2 inhibitor for at least 12 weeks have also been enrolled.

Up to 30% of IgAN patients with persistent higher levels of proteinuria of ≥1 g/day progress to kidney failure within ten years. Effective therapies are needed to slow down the progression of kidney failure.

Novartis is continuing the development of three promising treatments for IgAN to address the unmet needs of patients with the condition. Based on the results of an interim analysis of proteinuria levels, Novartis intends to submit an application for potential accelerated approval in the U.S. in 2024, and the study is expected to conclude with final results reported in the first quarter of 2026.

“These positive topline Phase III data showcase the potential of atrasentan to improve outcomes for patients with IgAN by demonstrating clinically meaningful proteinuria reduction,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis.

Our development portfolio of three highly differentiated late-stage therapies, including investigational iptacopan with its recent positive Phase III results and investigational zigakibart, has the potential to provide much-needed treatment options for people living with IgAN. These therapies hold great promise for addressing the debilitating effects of this disease, they said.

Reference:

Novartis. Novartis investigational atrasentan Phase III study demonstrates clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy (IgAN). News. October 30, 2023. Accessed October 30, 2023.