布地奈德缓释胶囊治肾病：3期NefigArd试验显奇效！

IgA nephropathy (IgAN) accounts for about 45%-50% of primary glomerular diseases in my country. Some patients have good prognosis, but there are still some patients who can develop end-stage renal disease (ESRD) 10-20 years after diagnosis, which is one of the main causes of ESRD. In addition to being widely used to treat Crohn's disease, it has also completed Phase II clinical studies for IgA nephropathy and has been granted orphan drug status by the European Union and the US FDA. Let’s introduce the effect of budesonide sustained-release capsules in treating kidney disease.

Research purpose

The therapeutic potential of a novel targeted-release formulation of oral budesonide extended-release capsules for the treatment of IgA nephropathy (IgAN) was first demonstrated by the Phase 2b NEFIGAN trial. To validate these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of budesonide extended-release capsules (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progression to renal failure (ClinicalTrials.gov: NCT03643965) [1].

NefIgArd was a multicenter, randomized, double-blind, placebo-controlled, two-part trial. In Part A, 199 patients with IgAN received budesonide extended-release capsules or placebo for nine months and were observed for an additional three months. The primary endpoint of Part A was 24-hour urine protein to creatinine ratio (UPCR) after 9 months. Secondary efficacy outcomes assessed included estimated glomerular filtration rate (eGFR) at 9 and 12 months and UPCR at 12 months.

result

At nine months, UPCR was reduced by 27% in the budesonide extended-release capsule group compared with placebo, while the eGFR preservation benefit was equivalent to a difference of 3.87 ml/min/1.73 m2 compared with placebo (both significant). Budesonide extended-release capsules were well tolerated, and most adverse events that occurred during treatment were mild to moderate in severity and reversible.

Conclusion

NefIgArd is therefore the first Phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the results of the Phase 2b budesonide extended-release capsule study.

References

[1]Barratt J, Lafayette R, Kristensen J, Stone A, Cattran D, Floege J, Tesar V, Trimarchi H, Zhang H, Eren N, Paliege A, Rovin BH; NefIgArd Trial Investigators. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int. 2022 Oct 18:S0085-2538(22)00836-5. doi: 10.1016/j.kint.2022.09.017. Epub ahead of print. PMID: 36270561.

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