Corcept Therapeutics: relacorilant

However, this analysis was not pre-specified in the statistical analysis plan, and in general, post-hoc analyses of a failed trial can be unreliable.

Additionally, your analysis was based on a small number of subjects and there was a large amount of missing data (only 8/16 subjects in the relacorilant arm and 13/17 subjects in the placebo arm were included).

A wash-out imputation method that we conducted during review of your application failed to demonstrate even nominal statistical significance for the estimated treatment effect of relacorilant compared to placebo in this subgroup.

Our results showed that the Least Squares mean change from baseline in 24-hour SBP was -7.7 mm Hg in the relacorilant arm, compared to -2.8 mm Hg in the placebo arm, resulting in a treatment difference between the two arms of -4.9 mm Hg (95% Cl: -15.3, 5.6; nominal p-value 0.36).

As substantial evidence of effectiveness was not demonstrated we are unable to conduct a final benefit risk assessment for relacorilant for the proposed indication.

Hy's law criteria for severe DILI, four cases were assessed as probable DILI due to relacorilant, with one subject experiencing a significant alanine aminotransferase (ALT) elevation of 1952 U/L, representing more than 50 times the upper limit of normal.

Because there were only 303 subjects exposed (to at least one dose of relacorilant), identification of DILI cases in even 4 subjects is concerning and it remains possible that more DILI cases may occur in the larger population with longer exposure in post-approval settings.

Based on the currently available information, we cannot conclude that relacorilant has a favorable benefit risk assessment for the proposed indication.