Novartis has announced final results from the phase III ALIGN study supporting a slowing decline in kidney function in adults with IgA nephropathy (IgAN) who were treated with Vanrafia (atrasentan).
Vanrafia showed a difference of 2.39ml/min/1.73m2 in estimated glomerular filtration rate (eGFR) change from baseline versus placebo (two-sided p= 0.057) at week 136, four weeks after the end of study treatment.
Clinically meaningful results were observed with Vanrafia compared to placebo in eGFR change from baseline at the end of study treatment at week 132, and in the prespecified exploratory group of patients additionally receiving sodium-glucose co-transporter-2 (SGLT2) inhibitors. At the end of treatment at week 132, the eGFR change from baseline compared to placebo was 2.59ml/min/1.73 m2 (nominal two-sided p=0.039).
“Progressive and complex diseases such as IgAN present an urgent need for medicines that can target the different drivers of the disease. Vanrafia can be seamlessly integrated into patients’ existing treatment plans, with a consistent safety profile,” said Ruchira Glaser, global head, Cardiovascular, Renal & Metabolic Development Unit, Novartis. “We are pleased with today’s phase III ALIGN results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline.”
IgAN is a progressive autoimmune kidney disease, leading to glomerular inflammation, proteinuria, and a gradual decline in eGFR. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management.
The ALIGN study (NCT04573478) is a global, randomised, multicentre, double-blind, placebo-controlled phase III clinical trial comparing the efficacy and safety of Vanrafia versus placebo in patients with IgAN at risk of progressive loss of kidney function. In total, 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1g/day despite optimised RAS inhibitor treatment were randomised to receive once-daily, oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks.
The primary efficacy endpoint for the interim analysis (in 270 patients) was change in proteinuria, as measured by 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to 36 weeks. The key secondary endpoint for the final analysis is the change from baseline to 136 weeks in kidney function as measured by eGFR. Other secondary efficacy endpoints as well as safety and tolerability are also assessed.
