The FDA warned Corcept Therapeutics that it would face significant hurdles if it submitted its lead rare disease asset for approval, contradicting the biotech’s claims that the candidate’s eventual rejection came as a shock.
In the updated complete response later (PDF), originally dated to Dec. 30 and published on Jan. 28, the FDA said that it cautioned Corcept “on several occasions of our concerns about the adequacy of the clinical development program” for relacorilant in Cushing’s syndrome, a hormonal condition caused by prolonged exposure to elevated cortisol.
These warnings came during meetings before Corcept submitted its new drug application, the agency said, and went so far as to alert the biotech “to expect significant review issues if you were to submit your application.”
Despite these warnings, Corcept CEO Joseph Belanoff, M.D., responded to the rejection on Dec. 31 by saying the company was “surprised and disappointed by this outcome.”
Corcept did not respond to a request for comment from Fierce Biotech.
The cortisol-focused company’s stock took a dip on the news, hitting a low of $37.26 per share Friday following the previous day’s close of $44.61. As of 1:30 p.m. ET, the stock had stabilized to $39.34 per share.
Corcept has been trading about 50% lower since relacorilant’s rejection, tumbling from the New Year’s Eve price of $70.20 per share.
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In its post-rejection release, Corcept said that the FDA “acknowledged that Corcept’s pivotal Grace trial met its primary endpoint.” The FDA did acknowledge this in the CRL, but also said that the result “likely overestimates the treatment effect of relacorilant in the intended population” because only 45% of the trial’s enrolled patients moved from the open-label part to the randomized part, with 39% of patients leaving the study during the open-label component.
In another phase 3 trial of relacorilant, called Gradient, the candidate failed the primary endpoint of improving systolic blood pressure in patients with Cushing’s syndrome and other cortisol-related diseases, the FDA noted in the letter. Positive results from a post-hoc analysis conducted by Corcept specifically in patients with hypertension and Cushing’s syndrome are unreliable, the regulator added, because the trial failed and because “your analysis was based on a small number of subjects and there was a large amount of missing data.”
The FDA’s own analysis of this data “failed to demonstrate even nominal statistical significance for the estimated treatment effect of relacorilant compared to placebo in this subgroup,” the agency said in the letter.
Corcept is also testing relacorilant, an antiglucocorticoid, in multiple cancer indications. The biotech announced on Jan. 22 that the molecule had scored a win in a phase 3 trial in platinum-resistant ovarian cancer, improving median survival to 16 months when given with nab-paclitaxel chemotherapy, compared to 11.9 months for nab-paclitaxel alone.
In the past, the Securities and Exchange Commission has not taken kindly to biotechs misrepresenting their communications with the FDA. On Jan. 20, the SEC fined two former executives from Spero Therapeutics over their repeated claims that Spero’s lead antibiotic candidate had hit its efficacy goals in a phase 3 trial, despite being told otherwise by the FDA.
The Spero execs neither admitted nor denied that they committed any wrongdoing as part of their settlement with the SEC.
Asked if the Commission plans to investigate Corcept, an SEC spokesperson told Fierce that the agency “does not comment on the existence or nonexistence of a possible investigation.”