On December 31 of last year, the U.S. Food and Drug Administration (FDA) rejected Corcept Therapeutics’ application for relacorilant, an oral glucocorticoid receptor agonist developed to treat hypercortisolism. The company had previously described the decision as unexpected. However, according to a complete response letter made public on Friday, the FDA had warned Corcept about major concerns during early discussions.
The FDA stated in its letter: “During the pre-submission meetings, we informed you on several occasions of our concerns about the adequacy of the clinical development program to assess the effect of relacorilant on hypertension in the intended population.” The agency also told Corcept that it could “expect significant review issues” if it proceeded with its application.
Corcept supported its submission with results from two Phase III studies—GRACE and GRADIENT. In May 2024, data from the GRACE trial showed that relacorilant met its primary endpoint by significantly improving blood pressure control compared to placebo. Despite this result, the FDA pointed out that “the analysis was conducted in a highly enriched population” and cautioned that this might have led to an overestimation of relacorilant’s benefit in broader patient groups.
For additional evidence, Corcept submitted data from the GRADIENT study. The FDA noted that this trial did not meet its main objective.
Another concern raised by regulators involved cases of drug-induced liver injury identified during their review. While none were classified as severe, four instances were considered probably related to relacorilant use. The FDA wrote: “Based on the currently available information, we cannot conclude that relacorilant has a favorable benefit risk assessment for the proposed indication.”
The agency advised Corcept to produce new clinical data demonstrating both efficacy and safety for patients with hypercortisolism and recommended developing a strategy to manage potential liver injury risks.
It remains uncertain whether Corcept will undertake further studies needed for approval. CEO Joseph Belanoff commented after receiving notice of rejection: “We are confident we will find a way to get relacorilant to the patients it could help.”
