New Biomarker, Subgroup Analyses of Phase 3 NefIgArd Trial for Budesonide

Jonathan Barratt, PhD, FRCP

Credit: George Clinical

STADA and Calliditas Therapeutics announced the presentation of new biomarker and subgroup analyses from the phase 3 NefIgArd study of budesonide (Nefecon), currently marketed as Tarpeyo, in adults with primary immunoglobulin A nephropathy (IgAN).

Announced on September 29, 2023, study data revealed patients treated with budesonide 16 mg/day exhibited a statistically significant decrease in IgA-containing immune complex levels, B-cell activating factor (BAFF), a proliferation inducing ligand (APRIL), soluble B-cell maturation antigen (sBCMA), CXC chemokine ligand 5 (CXCL5), and C-C Motif Chemokine Ligand 13 (CCL13), with preservation of kidney function observed in both Asian and White ancestry subgroups.¹

“We are proud to have showcased new data at this year’s International Symposium on IgAN in Tokyo,” said Richard Phillipson, Chief Medical Officer at Calliditas.¹ “Taken together, the positive findings from our biomarker and patient subgroup analyses from our Phase 3 NefIgArd study indicate that Nefecon treatment results in a coordinated immunological response with the potential to modulate the intestinal immune network responsible for IgA production. These additional findings further reinforce the potential of TARPEYO in enabling physicians to proactively manage and potentially mitigate the impact of the disease by targeting the source and slowing kidney function decline.”

An oral, delayed-release formulation, budesonide targets mucosal B-cells present in the ileum responsible for the production of galactose-deficient IgA1 antibodies causing IgA nephropathy. On December 15, 2021, the US Food and Drug Administration (FDA) approved budesonide to reduce proteinuria in adults with IgAN at risk of rapid disease progression under accelerated approval.² The FDA granted priority review for its full approval on August 18, 2023, with an expected Prescription Drug User Fee Act goal date of December 20, 2023.³

A randomized, double-blind, placebo-controlled, phase 3 study, NefIgArd evaluated the efficacy and safety of budesonide 16 mg once daily versus placebo in adult patients with primary IgAN as an addition to optimized renin-angiotensin system inhibitor therapy. Part A of the study included a 9-month blinded treatment period and a 3-month follow-up period. The primary endpoint was urine protein to creatinine ratio and estimated glomerular filtration rate was a secondary endpoint. Part B included a 12-month observational period off drug and assessed estimated glomerular filtration rate over the entire 2-year period for patients who were treated with the budesonide or placebo regimen in Part A.¹

To be included in the study, participants were required to be aged ≥18 years, have biopsy-verified IgA nephropathy, urine protein creatinine ratio ≥1 g/24hr, estimated glomerular filtration rate ≥35 mL/min per 1.73 m2 and ≤90 mL/min per 1.73 m2, and have a background of optimized and stable renin-angiotensin system inhibitor therapy.⁴ In total, 364 patients were enrolled in the study and randomized in a 1:1 ratio into budesonide 16 mg/day orally or placebo treatment groups and treated for 9 months daily.⁵

Positive topline results were announced on March 12, 2023.⁵ Results of the full 2-year trial, which were presented at the 17th International Symposium on IgA Nephropathy, indicated a statistically significant benefit of budesonide over placebo in estimated glomerular filtration rate over the 2-year study period, a clinically significant reduction in proteinuria durable for the entire 15-month follow-up period off the study drug, and a decrease in microhematuria at follow up visits.¹

“These data show the kidney function protection delivered by Nefecon and demonstrate that the approach offers patients a truly disease modifying treatment with sustained reductions in proteinuria over two years and continued eGFR benefit,” stated Jonathan Barratt, PhD, FRCP, Mayer Professor of Renal Medicine at Leicester University.⁵ ”Importantly Nefecon was well tolerated and together with the proteinuria and eGFR data mean that Nefecon has cemented its place as a key treatment option for patients with IgA nephropathy at risk of progressive kidney function loss.”

References:

1. Callidatas Therapeutics. Calliditas Presents Data from the NefIgArd Phase 3 trial at the 17th International Symposium on IgA Nephropathy (IIgANN) Tokyo 2023. September 29, 2023. Accessed September 29, 2023. https://www.calliditas.se/en/calliditas-presents-data-from-the-nefigard-phase-3-trial-at-the-17th-international-symposium-on-iga-nephropathy-iigann-tokyo-2023/
2. Callidatas Therapeutics. FDA grants Calliditas Therapeutics Accelerated Approval of TARPEYO™ (budesonide) to Reduce Proteinuria in IgA Nephropathy. December 15, 2021. Accessed September 29, 2023. https://www.calliditas.se/en/fda-grants-calliditas-therapeutics-accelerated-approval-of-tarpeyo-budesonide-to-reduce-proteinuria-in-iga-nephropathy/
3. Callidatas Therapeutics. FDA grants priority review for full approval of TARPEYO for the treatment of IgA Nephropathy. August 18, 2023. Accessed September 29, 2023. https://www.calliditas.se/en/fda-grants-priority-review-for-full-approval-of-tarpeyo-for-the-treatment-of-iga-nephropathy/
4. Clinicaltrials.gov. Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy (Nefigard). July 18, 2023. Accessed September 29, 2023. https://clinicaltrials.gov/study/NCT03643965
5. Callidatas Therapeutics. Calliditas Announces Primary Endpoint Successfully Met in Phase 3 NefIgArd Trial Evaluating Nefecon[®] in IgA Nephropathy. March 12, 2023. Accessed September 29, 2023. https://www.calliditas.se/en/calliditas-announces-primary-endpoint-successfully-met-in-phase-3-nefigard-trial-evaluating-nefecon-in-iga-nephropathy/