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  "meta": {
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    "license": "https://open.fda.gov/license/",
    "last_updated": "2026-08-13",
    "results": {
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  "results": [
    {
      "letter_date": "01/28/2026",
      "approver_title": null,
      "file_name": "CRL_NDA219398_20260128.pdf",
      "letter_year": "2026",
      "approval_status": "Unapproved",
      "approver_name": "Center for Drug Evaluation and Research",
      "approver_center": [],
      "company_rep": "Christopher Golis",
      "company_address": "101 Redwood Shores Parkway\nRedwood City, CA 94065",
      "company_name": "Corcept Therapeutics",
      "text": "¢ IN U.S. FOOD & DRUG\n\nADMINISTRATION\n\nNDA 219398\nCORRECTED COMPLETE RESPONSE\n\nCorcept Therapeutics\n\nAttention: Christopher Golis\n\nVice President, Quality Assurance & Regulatory Affairs\n101 Redwood Shores Parkway\n\nRedwood City, CA 94065\n\nDear Christopher Golis:\nPlease refer to your new drug application (NDA) dated and received\n\n, and your amendments, submitted under\nfor relacorilant capsules.\n\nWe also refer to our complete response letter dated December 30, 2025, which\ncontained no errors but is being updated to respond to Concept's communication dated\n\nThis corrected action letter incorporates revisions for clarity. The effective action date\nwill remain December 30, 2025, the date of the original letter.\n\nWe have completed our review of this application, as amended, and have determined\nthat we cannot approve this application in its present form. We have described our\nreasons for this action below and, where possible, our recommendations to address\nthese issues.\n\nClinical and Statistical\n\n1. Substantial evidence of effectiveness\nTo support efficacy for the me)\n, you submitted the results of two phase 3 trials (CORT125134-455!\nand CORT125134-4562). For the following reasons, the provided evidence is not\nsufficient to demonstrate the effectiveness of relacorilant for the proposed indication.\n\n1 Trial CORT125134-455: Glucocorticoid Receptor Antagonism in the Treatment of Cushing's Syndrome:\nA Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety\nof Relacorilant\n\n2 Trial CORT125134-456: Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in\nPatients with Cortisol-Secreting Adrenal Adenomas or Hyperplasia: A Phase 3, Randomized, Double-\nBlind, Placebo-Controlled Study of the Efficacy and Safety of Relacorilant\n\nReference ID: 5735859\n\nNDA 219398\nPage 2\n\nA. CORT125134-455\n\nCORT125134-455 was conducted in subjects with endogenous Cushing’s\nsyndrome and concurrent hypertension (defined as mean systolic blood pressure\n2135 to $170 mm Hg and/or mean diastolic blood pressure 285 to\n\n<110 mm Hg, measured by ambulatory blood pressure monitor and no increase\nin doses of antihypertensive medications for at least 4 weeks prior to baseline\nassessment) and/or diabetes (DM)/impaired glucose tolerance (IGT). The trial\nincluded a 22-week single-arm, open-label treatment phase, which was followed\nby a 12-week placebo-controlled, randomized withdrawal phase. The primary\nendpoint of this trial was the loss of response with respect to hypertension from\nopen-label phase Week 22 to randomized-withdrawal phase Week 12, based on\n24-hour ambulatory blood pressure monitoring (ABPM), in subjects with baseline\nhypertension.\n\nWhile CORT125134-455 met its primary endpoint, the analysis was conducted in\na highly enriched population. Of the ™ subjects enrolled, 102 subjects had\nhypertension at baseline, of which 40 (39%) subjects discontinued the trial during\nthe open-label phase and only 46 (45%) subjects entered the randomized\nwithdrawal phase. As such, the observed treatment effect in the randomized\nwithdrawal phase likely overestimates the treatment effect of relacorilant in the\nintended population. We acknowledge that in the 22-week open-label period, in\nwhich all subjects were treated with relacorilant, the mean (SD) change from\nbaseline in systolic blood pressure at the end of the open-label phase was -5.2\n(10.4) mm Hg (with missing data imputed using a return-to-baseline approach).\nHowever, we find this treatment estimate to be unreliable given the large amount\nof missing data. In addition, there was no control group with which to interpret the\nchange in blood pressure.\n\nCORT125134-456\n\nCORT125134-456 was a randomized, double-blind, placebo-controlled trial in\nsubjects with Autonomous Cortisol Secretion (ACS) and Cushing’s Syndrome,\nassociated with uncontrolled systolic hypertension and/or DM/IGT. However, the\ntrial did not meet its primary efficacy endpoint, defined as the mean change in\n24-hour average systolic blood pressure (SBP) based on 24-hour ABPM, from\nbaseline to Week 22 in subjects with systolic hypertension at baseline. In the {fj}\nsubjects with ACS and Cushing’s Syndrome and with hypertension at baseline\n{) in each arm), the mean change in 24-hour SBP from baseline was -5.8\n\nmmbg in the relacorilant arm and -5 mmHg in the placebo arm, resulting ina\nbetween-arm difference (relacorilant vs. placebo) of -0.85 mmHg (95% Cl: -6.7,\n4.9; p-value 0.77).\n\nWe acknowledge that you also conducted a post-hoc analysis of the primary\nendpoint in the 33 subjects with hypertension and Cushing’s Syndrome (16 in\n\nU.S. Food and Drug Administration\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nNDA 219398\nPage 3\n\nrelacorilant arm and 17 in placebo arm). Your analysis showed a nominally\nsignificant decrease in systolic blood pressure compared to placebo as follows:\nthe Least Squares mean change from baseline to Week 22 in systolic blood\npressure was -11.2 mm Hg in the relacorilant arm, compared to -0.8 mm Hg in\nthe placebo arm, resulting in a nominally significant difference between the two\narms of -10.4 mm Hg (95% Cl: -19.7, -1.2; nominal p-value 0.03). However, this\nanalysis was not pre-specified in the statistical analysis plan, and in general,\npost-hoc analyses of a failed trial can be unreliable. Additionally, your analysis\nwas based on a small number of subjects and there was a large amount of\nmissing data (only 8/16 subjects in the relacorilant arm and 13/17 subjects in the\nplacebo arm were included). A wash-out imputation method that we conducted\nduring review of your application failed to demonstrate even nominal statistical\nsignificance for the estimated treatment effect of relacorilant compared to\nplacebo in this subgroup. Our results showed that the Least Squares mean\nchange from baseline in 24-hour SBP was -7.7 mm Hg in the relacorilant arm,\ncompared to -2.8 mm Hg in the placebo arm, resulting in a treatment difference\nbetween the two arms of -4.9 mm Hg (95% Cl: -15.3, 5.6; nominal p-value 0.36).\n\nDuring the pre-submission meetings, we informed you on several occasions of our\nconcerns about the adequacy of the clinical development program to assess the\neffect of relacorilant on hypertension in the intended population including the design\nof CORT125134-455, and to expect significant review issues if you were to submit\nyour application.\n\n2. Benefit Risk Assessment\n\nAs substantial evidence of effectiveness was not demonstrated we are unable to\nconduct a final benefit risk assessment for relacorilant for the proposed indication.\nAfter conducting a thorough safety review, we concluded that relacorilant is\nassociated with drug induced liver injury (DILI). While no subjects met the traditional\nHy's law criteria for severe DILI, four cases were assessed as probable DILI due to\nrelacorilant, with one subject experiencing a significant alanine aminotransferase\n(ALT) elevation of 1952 U/L, representing more than 50 times the upper limit of\nnormal. Post-market data indicate that patients with ALT >1000 U/L due to DILI have\nincreased risk for developing jaundice (Hy’s law) which carries a higher liver related\nfatality risk. The temporal relationship of the adverse event to study drug initiation,\nand the lack of alternative etiology identified despite extensive work-up, suggests\nthis event was likely related to relacorilant treatment. The continued rise in liver\nenzyme levels after relacorilant discontinuation does not rule out relacorilant as an\ninstigating factor, as drug-induced liver injury can persist for weeks to months after\n\n3 Chalasani N, et al. Prognostic significance of very high and towering peak alanine aminotransferase\n(ALT) values with normal or near normal total bilirubin in patients with idiosyncratic drug-induced liver\ninjury. J of Hepatology. 82: Suppl 1, S97-FRI-153. (2025)\n\nU.S. Food and Drug Administration\n\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nNDA 219398\nPage 4\n\nthe offending drug is discontinued. Because there were only 303 subjects exposed\n(to at least one dose of relacorilant), identification of DILI cases in even 4 subjects is\nconcerning and it remains possible that more DILI cases may occur in the larger\npopulation with longer exposure in post-approval settings.\n\nBased on the currently available information, we cannot conclude that relacorilant\nhas a favorable benefit risk assessment for the proposed indication. We. also\nreviewed the exploratory evidence for benefits aside from\n\nsuch as body weight and blood glucose control and were not persuaded that such\nbenefits were observed in your clinical development program.\n\nPath forward\nTo address these deficiencies, you will need to provide new clinical data to demonstrate\nthat relacorilant treatment results in a clinically meaningful »\n\n. In addition, the benefits\ndemonstrated to be attributable to relacorilant must outweigh its risks.\n\nWe also recommend that you submit a proposal for adequate DILI risk mitigation\nstrategies including appropriate labeling warnings, routine monitoring requirements,\nenhanced pharmacovigilance, and post-market evaluation.\n\nAdditionally, from a mechanistic standpoint, glucocorticoid receptor antagonism would\nbe expected to improve other aspects of\n\nAlthough you may continue to focus on only, relacorilant\nmay have benefit for the broader indication of treatment of . If you\nchoose to investigate this hypothesis further, we are open to meeting with you to\ndiscuss a feasible controlled clinical trial design using a novel endpoint such as a\ncomposite of signs and symptoms of .\n\n() (4),\n() 4)\n\nPRESCRIBING INFORMATION\n\nWe reserve comment on the proposed labeling until the application is otherwise\nadequate. We encourage you to review the labeling review resources on the\nPrescription Drug Labeling Resources* and Pregnancy and Lactation Labeling Final\nRule® websites, including regulations and related guidance documents and the Selected\nRequirements for Prescribing Information (SRPI) — a checklist of important format items\nfrom labeling regulations and guidances.\n\n4 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources\n5 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-\nfinal-rule\n\nU.S. Food and Drug Administration\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nNDA 219398\nPage 5\n\nCARTON AND CONTAINER LABELING\n\nWe reserve comment on the proposed labeling until the application is otherwise\nadequate.\n\nPROPRIETARY NAME\n\nPlease refer to our correspondence dated, me) , which addresses the\nproposed proprietary name, {/\"). This name was found conditionally acceptable\npending approval of the application in the current review cycle. Please resubmit the\nproposed proprietary name when you respond to all of the application deficiencies that\nhave been identified in this letter.\n\nSAFETY UPDATE\n\nWhen you respond to the above deficiencies, include a safety update as described at\n21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical\nand clinical studies/trials of the drug under consideration regardless of indication,\ndosage form, or dose level.\n\n(1) Describe in detail any significant changes or findings in the safety profile.\n(2) When assembling the sections describing discontinuations due to adverse\n\nevents, serious adverse events, and common adverse events, incorporate new\nsafety data as follows:\n\ne Present new safety data from the studies/clinical trials for the proposed\nindication using the same format as in the original submission.\n\ne Present tabulations of the new safety data combined with the original\napplication data.\n\ne Include tables that compare frequencies of adverse events in the original\napplication with the retabulated frequencies described in the bullet above.\n\ne For indications other than the proposed indication, provide separate tables for\nthe frequencies of adverse events occurring in Clinical trials.\n\n(3) Present a retabulation of the reasons for premature trial discontinuation by\nincorporating the drop-outs from the newly completed trials. Describe any new\ntrends or patterns identified.\n\nU.S. Food and Drug Administration\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nNDA 219398\nPage 6\n\n(4) Provide case report forms and narrative summaries for each subject who died\nduring a Clinical trial or who did not complete a trial because of an adverse event.\nIn addition, provide narrative summaries for serious adverse events.\n\n(5) Describe any information that suggests a substantial change in the incidence of\ncommon, but less serious, adverse events between the new data and the original\napplication data.\n\n(6) Provide updated exposure information for the clinical studies/trials (e.g., number\nof subjects, person time).\n\n(7) Provide a summary of worldwide experience on the safety of this drug. Include\nan updated estimate of use for drug marketed in other countries.\n\n(8) Provide English translations of current approved foreign labeling not previously\nsubmitted.\n\nOTHER\n\nWithin one year after the date of this letter, you are required to resubmit or take other\nactions available under 21 CFR 314.110. If you do not take one of these actions, we\nmay consider your lack of response a request to withdraw the application under\n\n21 CFR 314.65. You may also request an extension of time in which to resubmit the\napplication.\n\nA resubmission must fully address all the deficiencies listed in this letter and should be\nclearly marked with \"RESUBMISSION\" in large font, bolded type at the beginning of the\ncover letter of the submission. The cover letter should clearly state that you consider\nthis resubmission a complete response to the deficiencies outlined in this letter. A partial\nresponse to this letter will not be processed as a resubmission and will not start a new\nreview cycle.\n\nYou may request a meeting or teleconference with us to discuss what steps you need to\ntake before the application may be approved. If you wish to have such a meeting,\nsubmit your meeting request as described in the draft guidance for industry Formal\nMeetings Between the FDA and Sponsors or Applicants of PDUFA Products.\n\nThe product may not be legally marketed until you have been notified in writing that this\napplication is approved.\n\nU.S. Food and Drug Administration\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nNDA 219398\n\nPage 7\nIf you have any questions, contact\n\nSincerely,\n\n{See appended electronic signature page}\n\nCenter for Drug Evaluation and Research\n\nU.S. Food and Drug Administration\nSilver Spring, MD 20993\nwww.fda.gov\n\nReference ID: 5735859\n\nSignature Page 1 of 1\n\nThis is a representation of an electronic record that was signed\nelectronically. Following this are manifestations of any and all\nelectronic signatures for this electronic record.\n\n(b) (4)\n\n01/28/2026 03:16:34 PM\n\nReference ID: 5735859\n",
      "application_number": [
        "NDA 219398"
      ],
      "letter_type": "COMPLETE RESPONSE"
    }
  ]
}