NefIgArd: DESIGNED TO EVALUATE KIDNEY FUNCTION (eGFR) OVER 2 YEARS WITH 9 MONTHS OF TREATMENT1
Primary endpoint at full study completion: time-weighted average of eGFR over 2 years (N=364)1*
Key inclusion criteria2,3
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.
Select baseline characteristics2
| Patient characteristics | TARPEYO + RASi | RASi alone |
|---|---|---|
Median age (range) |
43 (36 to 50) | 42 (34 to 49) |
Median baseline UPCR (interquartile range) |
1.28 (0.90 to 1.76) | 1.25 (0.88 to 1.74) |
Median baseline eGFR (interquartile range) |
56.14 mL/min/ 1.73 m2 (45.50 to 70.97) |
55.11 mL/min/ 1.73 m2 (45.96 to 67.74) |
<60 mL/min per 1.73 m2 |
109 (60%) |
109 (60%) |
≥60 mL/min per 1.73 m2 |
73 (40%) |
73 (40%) |
Median time from IgAN diagnosis (interquartile range) |
2.4 years (0.6 to 6.9) | 2.6 years (0.6 to 6.5) |
- Blood pressure was well controlled at study entry (recommended target of <125/75 mmHg)1
- Majority of patients had not been on prior steroid therapy1
- On average, patients were in Stage 3 CKD at baseline2,4
TARPEYO was studied under the name Nefecon.
*The primary endpoint was UPCR at 9 months compared to baseline (N=199).1
THE ONLY FDA-APPROVED TREATMENT SHOWN TO STABILIZE eGFR WHILE ON THERAPY IN A PHASE 3 IgAN TRIAL1,3,5
Time-weighted average of eGFR showed a difference of 5.05 mL/min/1.73 m2 over 2 years in favor of TARPEYO vs RASi alone2*
LS mean change in eGFR of +1.5 mL/min/1.73 m2 at 9 months1
LS mean change in eGFR from baseline to 2 years (95% CI; p<0.0001)1†
less kidney function loss at 2 years1,3§
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).1
†Estimated from a mixed-model, repeated-measures analysis using untransformed data up to 24 months, regardless of use of rescue medications.1
‡Not all patients in the full analysis set (FAS) contributed data at each time point.1
§Calculated as relative reduction (9.4% TARPEYO + RASi vs 20.3% RASi alone).1,3
POST HOC SUBANALYSIS:CONSISTENT eGFR RESULTS REGARDLESS OF BASELINE UPCR6
Patients with baseline UPCR <0.8 g/g qualified for the trial if their proteinuria levels were ≥1 g/d6
Mean (±SE) absolute change in eGFR baseline UPCR < 0.8 g/g*†
Mean (±SE) absolute change in eGFR baseline UPCR ≥ 0.8 g/g*†
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).6
†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).6
‡Not all patients contributed data at each time point.
REDUCTIONS IN Gd-IgA1 WERE SEEN WITH TARPEYO3*
In NefIgArd, serum Gd-IgA1 was significantly reduced at months 3, 6, and 93,7
Change in Gd-IgA1 with TARPEYO + RASi vs RASi alone3
Data are exploratory. Clinical significance has not been established. Small sample sizes of a specific patient group are limitations of these analyses. Additional longitudinal studies of more diverse patient cohorts are needed to validate findings.
52% REDUCTION IN UPCR ACHIEVED AT 12 MONTHS1
- A substantial reduction in UPCR (28%) occurred between months 6 and 121
LS mean percent change in UPCR (g/g) from baseline1*†
Proteinuria response to therapy 1*†
Managing treatment expectations and adherence on therapy
- Evaluate therapy response at 6 months or after as patients start to see reductions in proteinuria during this time1
- Patients should complete the full 9-month course of therapy to see the full clinical benefits1
- Most adverse reactions were mild or moderate and resolved within 3 months of completing therapy, not resulting in substantial discontinuation. Proactively setting expectations is important for supporting adherence to therapy1,3
*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
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; AUC=area under the curve; CI=confidence interval; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; FAS=full analysis set; Gd-IgA1=galactose-deficient IgA1; KDIGO=Kidney Disease: Improving Global Outcomes; LS=least squares; RASi=renin-angiotensin system inhibitor; SE=standard error; UPCR=urine protein-to-creatinine ratio.
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 randomised phase 3 trial. Lancet. 2023. https://doi.org/10.1016/S0140-6736(23)01554-4 3. Data on file. Calliditas Therapeutics AB. 4. National Kidney Foundation. Stages of Chronic Kidney Disease (CKD). Accessed June 10, 2025. https://www.kidney.org/kidney-topics/stages-chronic-kidney-disease-ckd 5. 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 6. 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. 7. Cotton V, Nawaz N, Molyneux K, et al. Analysis of the NefIgArd Part A study population confirms Nefecon suppresses circulating levels of IgA-containing immune complexes in IgA nephropathy. Leicester IgAN research group. Poster presented at IIgANN Congress; September 28-30, 2023.