Shares of Corcept Therapeutics dropped sharply after the U.S. Food and Drug Administration released a corrected complete response letter (CRL) that said the regulator had cautioned the company "on several occasions" against submitting its application for relacorilant.
The corrected CRL, dated January 28, reiterated that the FDA had told Corcept to "expect significant review issues" if it continued with the submission. The regulator commonly issues CRLs when it decides not to approve a drug.
The filing under review concerned relacorilant, an oral therapy intended to address hypertension in patients with Cushing's syndrome, a rare disorder tied to prolonged elevated cortisol activity.
According to the corrected letter, the main clinical trial did not demonstrate that relacorilant performed better than placebo - the agency described there was virtually no difference between the treatment and placebo groups. In addition to the efficacy shortfall, the FDA cited serious liver safety issues: four patients were identified with probable drug-induced liver injury, and one patient had liver enzyme readings exceeding 50 times the upper limit of normal.
UBS analyst Ashwani Verma characterized the language in the CRL as unusually strong, saying it is "rare for FDA to use such language" in a rejection letter. Verma also reported that company management told him they had moved ahead with the submission following the guidance of their regulatory advisors, but that the FDA appeared to hold a firm position based on the CRL's wording.
The corrected CRL follows an earlier version dated December 30. The January 28 update was issued after additional communications from the company. The corrected letter was posted on the FDA's website on Thursday afternoon at about 4 p.m. ET, according to Verma.
Under the terms set out in the CRL, Corcept has one year to resubmit its application and complete certain other actions identified by the agency. The letter warned that the FDA would consider a lack of response to be a request to withdraw the application.
Corcept did not immediately respond to a request for comment.
Context and market reaction
Following the corrected CRL, Corcept's stock fell by 16% on Friday. The market move reflects investor concern over both the absence of demonstrable efficacy in the pivotal study and the emergence of significant safety signals related to liver injury.
What remains in play
- Corcept has up to one year to address the issues cited and resubmit its application.
- The FDA's explicit statements that it had warned the company against submitting add weight to regulatory hurdles ahead.
- Unresolved efficacy and safety findings create uncertainty about the likelihood of eventual approval.