Budesonide Reduces eGFR Decline, Effect Could Prevent Clinical Events in IgA Nephropathy

Data from a pair of studies presented at the American Society of Nephrology Kidney Week 2023 are offering further insight into the potential of budesonide delayed-release capsules (Tarpeyo) in the management of primary IgA nephropathy.

At the meeting, clinicians were given new insight into the 2-year data from the phase 3 NefIgArd Study and a modeling study extrapolating the potential benefits of budesonide delayed-release capsules among this patient population as the agent’s December 2023 PDUFA date approaches.^1,2,3

eGFR decline from 2-year NefIgArd Data

After the release of full trial results in The Lancet in August 2023, a study from Kidney Week 2023 presented by Richard Lafayette, MD, of founder and director of the Stanford Glomerular Disease Center, described the effects of budesonide delayed-release capsules compared to placebo therapy on eGFR decline at 2 years among patients in the trial. Of note, this analysis included all 364 patients from the full analysis set of the trial.¹

Results of the analysis indicated 21.4% of the placebo arm and 11.5% of the budesonide arm experienced an eGFR decline of 30% or greater. Further analysis suggested time to a confirmed 30% reduction was significantly delayed with budesonide relative to placebo (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.75]; P=.0014). Investigators also noted a predefined supplementary analysis with rescue medication use included as an event yielded a similar result (HR, 0.51).¹

Long-Term Modeling Study²

Another study at Kidney Week 2023, presented by Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, detailing the results of a modeling study based on 2-year eGFR total slope from NefIgArd aimed at predicting long-term clinical outcomes in IgA nephropathy. With the observed 2-year total eGFR slope of 2.78 mL/min/1.73m2 per year (95% CI, 1.39–4.17), investigators designed a linear regression model to examine treatment effects for the change in 2-year eGFR total slope and the log HR of clinical outcomes, based on a meta-analysis involving more than 60,000 chronic kidney disease patients.²

Of the 364 NefIgArd patients, investigators matched 352 to a cohort of 866 unique records from Leicester General Hospital. Results of the modeling study indicated the total slope observed in NefIgArd translated to a log HR for clinical outcomes of 0.38 (95% CI, 0.21–0.63) relative to placebo. Further analysis suggested the median time to clinical outcome was 9.6 years in the standard of care groups and 22.4 years in the budesonide arm (median delay 12.8 [95% CI 4.8–27.9] years). Additionally, investigators highlighted 24% of the budesonide group was expected to experience a clinical outcome within 10 years compared to 52% of the standard of care group.²

Check out our interview with Barratt for more on budesonide delayed-release capsules in the management of IgA nephropathy.

Relevant disclosures for Barrett included Calliditas Therapeutics, Alnylam Pharmaceuticals, Travere Therapeutics, Chinook Therapeutics, Novartis, and others.

References:

1. Lafayette RA, Kristensen J, Stone AM, et al. eGFR Decline in Patients with IgA Nephropathy Treated with Nefecon or Placebo: Results from the 2-Year NefIgArd Phase 3 Trial. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
2. Barrett J, Stone AM, Reich HN, Lafayette RA. Modeling Based on NefIgArd Two-Year eGFR Total Slope Predicts Long-Term Clinical Benefit of Nefecon in a Real-World IgA Nephropathy (IgAN) Population. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
3. Calliditas Therapeutics. FDA Grants Priority Review for full approval of Tarpeyo for the treatment of IGA nephropathy. FDA grants priority review for full approval of TARPEYO for the treatment of IgA Nephropathy. August 18, 2023. Accessed November 4, 2023. https://www.prnewswire.com/news-releases/fda-grants-priority-review-for-full-approval-of-tarpeyo-for-the-treatment-of-iga-nephropathy-301904398.html.