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Abstract: TH-PO1029

Systemic GCS Exposure from Nefecon Administration, Estimated from Suppression of Endogenous Cortisol Production

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Jerling, Markus, Markus Jerling Consultancy AB, Stockholm, Sweden
  • Rendón-Rapp, Sofia, Calliditas Therapeutics AB, Stockholm, Sweden
  • Kristensen, Jens, Calliditas Therapeutics AB, Stockholm, Sweden
Background

Nefecon is a unique two-step release oral formulation for the treatment of IgAN by a targeted delivery of budesonide to the Peyer’s patches in the lower small intestine, aiming at local immunosuppression of B-cells responsible for the production of secretory galactose-deficient IgA antibodies. In a phase 2b study once daily oral treatment with Nefecon for 9 months reduced proteinuria and stabilised eGFR. Budesonide has a high first-pass metabolism of 90% resulting in limited systemic GCS exposure. The potency of steroids can be assessed by the HPA-axis derived suppression of endogenous cortisol production.

Methods


A study in 24 healthy subjects compared the change in serum cortisol levels over 24 hours after single doses of 8 mg NEFECON, 16 mg NEFECON, and 9 mg ENTOCORT in a randomised cross-over design. Urine cortisol excretion over 24 hours and plasma budesonide pharmacokinetic pqqarameters were also compared.

Results


A 9 mg dose of ENTOCORT corresponded to 11.7 mg of NEFECON for serum cortisol suppression. NEFECON 16 mg and ENTOCORT 9 mg caused similar decreases in urine cortisol excretion. Budesonide AUC(0-24) was comparable for NEFECON and ENTOCORT per mg dose but with approximately double Cmax values for NEFECON.

Conclusion


The higher ratio Cmax / AUC for Nefecon compared to Entocort demonstrate a shorter duration of release with a longer period of low budesonide plasma concentrations during the 24 hour period. The net effect is a lower cortisol suppression per mg dose. A published study has shown that 29 mg of Entocort is equivalent to 20 mg of prednisolone for plasma cortisol suppression. The combined studies indicate that 16 mg of Nefecon is equivalent to 8 mg of prednisolone for plasma/serum cortisol suppression.

Results