Budesonide Maintains IgA Nephropathy Kidney Failure Reduction, Quality of Life at 2 Years

Richard Lafayette, MD

Credit: LinkedIn

Daily 16 mg oral targeted-release budesonide capsule (Nefecon) provided more preserved kidney function without worse impact to quality of life (QoL) compared to placebo in patients with immunoglobulin A (IgA) nephropathy over 2 years, according to findings from a pair of late-stage trials.

Data from the phase 3 NeflgArd trial, presented this week at the ISN World Congress of Nephrology 2024 in Buenos Aires, Argentina, showed the novel therapy was associated with no clinically significant changes in any QoL domains per 36-Item Short Form Health Survey (SF-36) results compared to placebo. Combined with findings from NeflgArd that which also showed a reduced estimated glomerular filtration rate (eGFR) change among patients receiving budesonide versus placebo over 2 years following a 9-months regimen, the data depict a promising benefit-risk profile associated with Calliditas Therapeutics’ investigative drug.

The findings were additionally accompanied by data from the World Congress showing benefit in kidney health for patients with IgA nephropathy regardless of low urine protein creatinine ratio (UPCR) levels at baseline and White or Asian patient background—a series of data from NeflgArd that depicts a more comprehensive clinical profile of budesonide over 2 years.

“We were pleased to share additional analyses from the 2-year phase 3 NeflgArd trial of Nefecon in IgAN at this year’s World Congress of Nephrology,” Richard Philipson, Chief Medical Officer of Calliditas, said in an accompanying statement. “These additional data further reinforce the impact of Nefecon across the entire study population, irrespective of baseline UPCR levels or patient’s racial and ethnic backgrounds.”

eGFR Decline Improvement

Led by Richard Lafayette, MD, professor of medicine at Stanford University, investigators conducted an assessment of 2-year outcomes for composite endpoint of time to confirmed 30% eGFR reduction or kidney failure among patients in the NeflgArd trial. Original eligibility in the trial included patients aged ≥18 years old with biopsy-confirmed primary IgA nephropathy; eGFR 35 – 90 mL/min per 1.73 m2; and UPCR ≥0.8 g/g or proteinuria ≥1 g per 24 hours, despite inhibition of RAS.

Patients had been randomized to a 9-month regimen of either daily 16 mg budesonide (n = 182) or placebo (n = 182), then observed off-drug for 15 months afterward. Lafayette and colleagues noted only 21 (12%) of patients treated with budesonide reached the primary endpoint of 30% reduced eGFR from baseline or kidney failure at 2 years, compared with 39 (21%) patients receiving placebo—indicating a 55% reduced risk of outcome with treatment (hazard ratio [HR], 0.45; 95% CI, 0.26 – 0.75).

Another 32 (18%) patients on budesonide required rescue therapy, versus 56 (31%) of patients on placebo (HR, 0.51; 95% CI, 0.33 – 0.79). Investigators noted that the treatment effect of budesonide was notable regardless of patient rescue medication and baseline UPCR levels. The team additionally wrote that tolerability and safety profiles for the therapy were consistent with known locally-acting oral budesonide use.

“The time from randomization to confirmed 30% eGFR reduction or kidney failure was significantly delayed with Nefecon versus placebo,” Lafayette and colleagues wrote. “These findings strongly indicate that Nefecon preserved kidney function and provide support for Nefecon as a disease-modifying therapy in patients with IgAN.”

QoL Consistency

In the QoL assessment, a team of investigators led by Jonathan Barratt, PhD, of the College of Medicine Biological Sciences and Psychology at University of Leicester, sought to interpret change in SF-36 assessment scores among the 2 arms of the NeflgArd trial at 9 and 24 months versus baseline.

The 36-item questionnaire assessed 8 subscales of QoL, including: physical function; role limitations due to physical health; bodily pain; general health perceptions; vitality; social functioning; role limitations due to emotional problems; and mental health. Scores from each subscale ranged from 0 – 100 points, with greater scores indicating better QoL.

Investigators observed that SF-36 scores were similar between the budesonide and placebo arms across all the QoL subscales at baseline. Thereafter, they observed neither clinically meaningful worsening nor improvement of SF-36 scores at the end of the treatment period (9 months) as well as the end of the 2-year observation period (24 months).

“These findings further support the benefit/risk profile of Nefecon, demonstrating that 9 months of treatment with Nefecon 16 mg/day did not result in changes in QoL at any measure, while providing significant benefit in preserving kidney function,” they concluded.

References

1. ^{Lafayette R, Kristensen J, Stone A, Floege J, et al. eGFR decline in patients with IgAN treated with Nefecon or placebo: Results from the 2-year NefIgArd Phase 3 trial. Poster presented at: ISN World Congress of Nephrology 2024. Buenos Aires, Argentina. April 13 – 16, 2024.}
2. ^{Barratt J, Kristensen J, Stone A, Floege J, et al. Nefecon effect on quality of life in patients with IgAN: SF-36 results from the Phase 3 NefIgArd trial. Poster presented at: ISN World Congress of Nephrology 2024. Buenos Aires, Argentina. April 13 – 16, 2024.}
3. ^{Kunzmann K. Investigative Oral Targeted Budesonide Significantly Improves Berger Disease Over 9 Months. HCPLive. Published August 17, 2023. https://www.hcplive.com/view/investigative-oral-targeted-budenoside-significantly-improves-berger-disease-9-months}
4. ^{Calliditas Therapeutics. Calliditas Therapeutics Presents Additional Data Analyses from the Phase 3 NeflgArd trial of Nefecon in Primary IgA Nephropathy at the ISN World Congress of Nephrology 2024. Press release. Published April 18, 2024. https://news.cision.com/calliditas-therapeutics/r/calliditas-therapeutics-presents-additional-data-analyses-from-the-phase-3-neflgard-trial-of-nefecon,c3963340}