Calliditas Said Primary Endpoint Met in Phase 3 Trial of Nefecon in IgA Nephropathy
March 13, 2023
Rare Daily Staff
Calliditas Therapeutics said topline results from the global, randomized, double-blind, placebo-controlled phase 3 clinical trial of Nefecon delayed release capsules versus placebo in patients with primary IgA nephropathy met its primary endpoint.
The latest results are from a data readout from Part B of the study and provide longer term data from the phase 3 NefIgArd trial, which read out topline data on Part A in November 2020. Based on the Part A data, Calliditas received accelerated approval from the U.S. Food and Drug Administration in December 2021 and conditional marketing authorization from the European Commission in July 2022, marking the first time a drug was approved for the treatment of IgAN in the United States and the European Economic Area.
On the basis of this new data, Calliditas plans to file for full approval from the FDA, and support filing for full approval with European Commission and the United Kingdom’s Medicines and Healthcare products Regulatory Agency during 2023 for patients with primary IgAN based on the phase 3 study population.
Primary immunoglobulin A nephropathy (IgA nephropathy, or IgAN, or Berger’s Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 are recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end-stage renal disease. IgAN most often develops between the late teens and late 30s.
Nefecon (Tarpeyo/Kinpeygo) is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. Nefecon was designed as a 4 mg delayed release capsule and is enteric coated so that it would remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies causing IgAN. It is unclear to what extent Nefecon efficacy is mediated via local effects in the ileum vs. systemic effects.
Nefecon demonstrated a highly statistically significant benefit over placebo in estimated glomerular filtration rate over the two-year period of nine-months of treatment with Nefecon or placebo and 15-months of follow-up off drug. Supportive two-year total analyses were statistically significant and clinically meaningful reflecting a sustained treatment benefit.
The eGFR benefit was observed across the entire study population, irrespective of urine protein-to-creatinine ratio (UPCR) baseline, which the company believes supports a regulatory filing for full approval in the study population. UPCR reductions observed were durable, reflecting a long-lasting treatment effect during the 15-month follow-up period off treatment.
The results indicate that Nefecon was generally well-tolerated, and the safety profile was consistent with that observed in Part A of the trial.
“This reflects sustained impact on kidney function across the entire study population with a treatment that was specifically designed to treat IgAN by downregulating pathogenic IgA1 antibodies at their presumed source and we believe this dataset supports regulatory filing for full approval based on the phase 3 study population,” said Calliditas CEO Renée Aguiar-Lucander.
Photo: Renée Aguiar-Lucander, CEO for Calliditas Therapeutics
Sign up for updates straight to your inbox.