eGFR
TARPEYO stabilized eGFR while on treatment, and reduced the loss of kidney function over 2 years1
Primary endpoint
Time-weighted average of eGFR change over 2 years1
- Statistically significant benefit of 5.05 mL/min/1.73 m2 at 2 years2*
- LS mean change in eGFR of +1.5 mL/min/1.73 m2 at 9 months1
LS mean change in eGFR from baseline over 2 years (95% CI; p<0.0001)1*†
The favorable effect of TARPEYO on eGFR was seen as early as month 3 and remained consistent over 2 years.1
The effect of TARPEYO on the long-term rate of decline in kidney function has not been established.1
*The primary endpoint for the interim analysis was UPCR at 9 months compared to baseline (N=199).
†Estimated from a mixed-model, repeated-measures analysis using untransformed data up to 24 months, regardless of use of rescue medications.1
‡Calculated as relative reduction (9.4% TARPEYO + RASi vs 20.3% RASi alone).1,3
§Not all patients in the full analysis set (FAS) contributed data at each time point.1
CI=confidence interval; eGFR=estimated glomerular filtration rate; LS=least squares; RASi=renin-angiotensin system inhibitor; UPCR=urine protein-to-creatinine ratio.
eGFR results were consistent across UPCR subgroups5
A post hoc subgroup analysis of eGFR over time in patients with UPCR ≥ or <0.8 g/g5
- Patients with baseline UPCR <0.8 g/g met trial eligibility criteria with proteinuria ≥1 g/d5
Mean (±SE) absolute change in eGFR in patients with baseline UPCR <0.8 g/g5*†
Mean (±SE) absolute change in eGFR in patients with baseline UPCR ≥0.8 g/g5*†
Small sample sizes and lack of multiplicity adjustments are limitations of these analyses. Results should be interpreted with caution. The clinical significance of these results is unknown.
*Estimated absolute change from baseline=baseline geometric mean for total x (geometric LS mean of post-baseline value/baseline value for each treatment arm –1).5
†Estimated absolute change from baseline=baseline geometric mean for total x (geometric LS mean of ratio of AUC over 2 years compared with baseline for each treatment arm –1).5
‡Not all patients contributed data at each time point.
AUC=area under the curve; SE=standard error.
UPCR
Durable UPCR reduction through 2 years1
Significant reduction with a 9-month fixed course of TARPEYO treatment1
LS mean percent change in UPCR (g/g) from baseline1*†
- 41% average reduction in UPCR during observational follow-up (month 12 to month 24) compared to baseline based on longitudinal mixed-effects model for repeated-measures model (95% CI: 32% to 49%)2§
*Estimated mean percentage change from baseline in UPCR with 95% CI estimated from a mixed-model, repeated-measures analysis of log-transformed post-baseline to baseline ratios, regardless of use of prohibited medications.1
†The interim analysis at 9 months with the first 199 patients showed a 31% reduction in UPCR in patients treated with TARPEYO vs RASi alone (95% CI: 16% to 42% reduction; p=0.0001).1
‡Not all patients in the FAS contributed data at each time point.1
§Data based on FAS of 364 patients.1
Study Design
The NefIgArd trial was designed to evaluate kidney function at 2 years after 9 months on treatment, as measured by eGFR1
Primary endpoint at full study completion: eGFR at 2 years (N=364)1*
Key inclusion criteria1,2
Adult patients with2:
- Biopsy-confirmed IgAN diagnosis
- Persistent proteinuria ≥1 g/day or UPCR ≥0.8 g/g in 2 consecutive measurements
- eGFR 35 to 90 mL/min/1.73 m2
- Receiving RASi therapy (ACEis and/or ARBs) at the maximum allowed/tolerated dose 3 months prior to randomization
Blood pressure and diabetes were well controlled and no prophylaxis with antibiotics was required.1,2
Baseline characteristics2
Select baseline characteristics1,2
- More than half of patients were younger than 45 years of age at study entry
- Diverse patient population across ethnic backgrounds†
- Blood pressure was well controlled at study entry (recommended target of <125/75 mmHg)
- Majority of patients had not been on prior steroid therapy
Select secondary efficacy endpoints2
- Composite endpoint of time from randomization to confirmed 30% reduction in eGFR (confirmed by 2 values over ≥4 weeks)
- Ratios of UPCR and UACR compared with baseline‡
- Proportion of patients without microhematuria during observational follow-up
*The primary endpoint for the interim analysis was UPCR at 9 months compared to baseline (N=199).1
†Of the 364 randomized patients evaluated for efficacy, 66% were male, 76% were Caucasian, 23% were Asian, and 20% were from North America. The median age was 43 years (range 20 to 73 years).1
‡Ratios were averaged over timepoints between 12 and 24 months, inclusive, after the first dose of study drug.2
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; UACR=urine albumin-creatinine ratio.
TARPEYO was studied under the name NEFECON.
REFERENCES: 1. TARPEYO. Prescribing Information. Calliditas Therapeutics AB; June 2024. 2. 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 randomized phase 3 trial. Lancet. 2023;402(10405):825-936. http://doi.org/10.1016/S0140-6736(23)01554-4 3. Data on file. Part B. Calliditas Therapeutics AB. 4. Barratt J, Lafayette RA, Rovin BH, Fellström B. Budesonide delayed-release capsules to reduce proteinuria in adults with primary immunoglobulin A nephropathy. Expert Rev Clin Immunol. 2023;19(7):699-710. doi:10.1080/1744666X.2023.2206119 5. Barratt J, et al. Nefecon treatment provides kidney benefits for patients with IgAN that extend to those with low levels of UPCR: A subanalysis of the Phase 3 NefIgArd trial. Presented at the International Society of Nephrology World Congress of Nephrology; April 13-16, 2024; Buenos Aires, Argentina. 6. National Kidney Foundation. Stages of Chronic Kidney Disease (CKD). https://www.kidney.org/kidney-topics/stages-chronic-kidney-disease-ckd. Accessed September 20, 2024.