Calliditas Therapeutics AB have announced publication in The Lancet of the full data from the Phase 3 NefIgArd Study with Nefecon (TARPEYO (budesonide) delayed release capsules/Kinpeygo) in adults with Primary IgA nephropathy (IgAN). The Phase 3 trial met the primary endpoint, estimated glomerular filtration rate (eGFR), with Nefecon demonstrating significant kidney protective effect over placebo.
“IgAN is a severe debilitating disease leading to end-stage kidney disease in more than 50% of the patients. The full results from NefIgArd study demonstrate the ability of Nefecon to slow kidney function deterioration and as such to slow down the disease progression and delay the need for dialysis and kidney transplantation,” said Jonathan M. Barratt, M.D., Mayer Professor of Renal Medicine. University of Leicester. “These results also support the key role of the gut immune system in the pathogenesis of IgAN and the differentiated effect of Nefecon treating the disease at its origin.”
The analysis published in The Lancet shows that Nefecon demonstrated a highly statistically significant and clinically relevant benefit compared to placebo in eGFR over the two-year period of 9-months of treatment with Nefecon and 15-months of follow-up off drug. After the two-year period, there was a 6.11 mL/min/1.73 m2 decline in eGFR in the Nefecon arm compared with a 12.0 mL/min/1.73 m2 decline in the placebo arm, corresponding to a difference in two-year eGFR total slope of 2.95 mL/min/1.73m2 per year (p<0·0001).
The reduction in UPCR observed with Nefecon treatment was durable, reflecting a long-lasting treatment effect during the 15-month follow-up period off treatment. Patients treated with Nefecon maintained a greater than 30% proteinuria reduction from the end of the 9-month treatment through the entire follow-up period, with a reduction in UPCR of over 50% observed at 12 months.
Nefecon was generally well tolerated, with the majority of treatment-emergent adverse events (TEAE) being mild or moderate, and with TEAEs leading to discontinuation of study drug in <10% of patients. Objective measures of mean weight and blood pressure showed non-clinically relevant changes.
"The data demonstrated supportive 2-year total slope analyses that were not only statistically significant but also clinically meaningful, showcasing a sustained treatment benefit. The eGFR benefit was observed across the entire study population, irrespective of baseline urine protein-to-creatinine ratio (UPCR),” said Richard Lafayette, M.D., F.A.C.P., Stanford Healthcare and lead author of the publication. “The sustained reduction of proteinuria and the protective effect on kidney function support the disease-modifying effect of Nefecon. These robust results provide new hope for patients and reinforce Nefecon's potential to make a meaningful difference in the lives of those affected by this challenging disease.”
Nefecon is currently approved under accelerated approval to reduce proteinuria in adults with Primary IgAN at risk of rapid disease progression, generally a UPCR ≥1.5 g/g. In June 2023, Calliditas submitted a supplemental new drug application (sNDA) to the United States Federal Drug Administration (FDA) seeking full approval based on the full NefIgArd study data. Calliditas is supporting its partner STADA Arzneimittel AG with the filing for full approval with the European Commission and the UK MHRA in 2H of 2023.