FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy

The US Food and Drug Administration has awarded full approval to budesonide (Tarpeyo) delayed release capsules for the treatment of immunoglobulin A nephropathy (IgAN).

Announced on December 20, 2023, the approval, which was awarded to Calliditas Therapeutics, makes budesonide delayed release capsules the first treatment to receive approval from the FDA for reducing the loss of kidney function in adults with primary IgAN.¹

“The evidence of sustained reductions in proteinuria and a clinically significant reduction in the loss of eGFR, which can help slow the progression towards dialysis or transplant care, highlights the potential of TARPEYO as a disease-modifying agent in IgAN,” said Richard Lafayette, MD, FACP, Stanford Healthcare.¹ “TARPEYO provides physicians and patients an effective treatment option to help improve disease outcomes.”

Designed to act at the gut mucosal level, the oral, targeted-release formulation of budesonide was granted accelerated approval by the FDA for proteinuria reduction in adults with primary IgAN at risk of rapid disease progression on December 17, 2021.2 Calliditas Therapeutics submitted a supplemental New Drug Application to the FDA on June 21, 2023, which was accepted and granted Priority Review shortly thereafter on August 18, 2023, based on the full data set from NefIgArd.^3,4

A randomized, double-blind, multicenter, phase 3 study, NefIgArd evaluated the efficacy and safety of once-daily budesonide 16 mg compared to placebo in adult patients with primary IgAN on optimized RASi therapy. For inclusion, patients were required to be ≥ 18 years of age and have primary IgAN, eGFR 35–90 mL/min per 1.73 m2, and persistent proteinuria, defined as urine protein–creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 h, despite optimized renin-angiotensin system blockade.⁵

A total of 364 patients were enrolled in the study and randomly assigned in a 1:1 ratio to 16 mg daily oral budesonide or placebo. The study was divided into 2 parts: Part A was a 9-month blinded treatment period followed by a 3-month follow-up period, and Part B was a 12-month observational follow-up period during which no study drug was administered.⁵

Results of the trial showed a statistically significant benefit of budesonide over placebo in estimated glomerular filtration rate (eGFR), with a 6.11 mL/min/1.73 m2 decrease in eGFR observed in the budesonide arm compared to a 12.0 mL/min/1.73 m2 decrease in the placebo arm, corresponding to a 2.95 mL/min/1.73m2 per year difference in 2-year eGFR total slope (P < .0001).¹

Of note, significant proteinuria reduction achieved with budesonide plus RASi at 9 months was durable and maintained throughout the 15-month off-drug period.¹

“This first-ever IgAN treatment to get a full approval based on kidney function represents a beacon of hope for the entire IgA nephropathy community and signifies a critical step forward in the battle against IgAN,” said Bonnie Schneider, director and cofounder of the IgAN Foundation.¹ “The foundation is elated and personally this is so rewarding and validating after a near 20-year journey since founding this volunteer-run organization to raise awareness and promote research for IgAN.”

References:

1. Calliditas Therapeutics announces full FDA approval of TARPEYO®, the only FDA-approved treatment for IGA nephropathy to significantly reduce the loss of kidney function. Calliditas Therapeutics AB. December 20, 2023. Accessed December 20, 2023. https://www.calliditas.se/en/calliditas-therapeutics-announces-full-fda-approval-of-tarpeyo-the-only-fda-approved-treatment-for-iga-nephropathy-to-significantly-reduce-the-loss-of-kidney-function/.
2. US Food and Drug Administration. FDA approves first drug to decrease urine protein in IgA nephropathy, a rare kidney disease. December 17, 2021. Accessed December 19, 2023. https://www.fda.gov/drugs/fda-approves-first-drug-decrease-urine-protein-iga-nephropathy-rare-kidney-disease
3. Calliditas Therapeutics. FDA grants priority review for full approval of TARPEYO for the treatment of IgA Nephropathy. Press Releases. August 18, 2023. Accessed December 19, 2023. https://www.calliditas.se/en/fda-grants-priority-review-for-full-approval-of-tarpeyo-for-the-treatment-of-iga-nephropathy/
4. Calliditas Therapeutics. Calliditas Therapeutics Submits Supplemental New Drug Application to U.S. Food and Drug Administration for Full Approval of TARPEYO[®]. June 21, 2023. Accessed December 19, 2023. https://www.calliditas.se/en/calliditas-therapeutics-submits-supplemental-new-drug-application-to-u-s-food-and-drug-administration-for-full-approval-of-tarpeyo/
5. Lafayette R, Kristensen J, Stone A, et al. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. The Lancet. https://doi.org/10.1016/S0140-6736(23)01554-4