CORT relacorilant

Cushing's syndrome · Corcept · NDA

Of 100 applications in this same position, about 40 get approved.

Until the FDA deadline73d

Base rate76%

Gap−36pts

PDUFA target date 2026-12-17the FDA may act earlier or later

Summary

FDA approval of relacorilant for Cushing's syndrome in this review cycle is put at 40%, below the 76% base rate for first-time applications from smaller companies. FDA rejected the drug in December 2025: it judged the efficacy evidence insufficient (the placebo-controlled GRADIENT trial missed its primary endpoint, p=0.77), found four probable cases of drug-induced liver injury, and asked for new clinical data. The resubmission contains only further analyses of the same trials. Approval remains a real possibility because FDA itself requested those analyses in April 2026 and accepted the resubmission for a six-month review. The same capsules were approved for ovarian cancer in March 2026, so manufacturing is not the obstacle. What the new analyses show is not public.

Recorded 2026-10-05 08:21 UTC · v1Proof ↓

Evidence · 8 items

Why 40%, not 76%

Indication

Cushing's syndrome (endogenous hypercortisolism); resubmission after a complete response letter. The first-cycle application sought hypertension secondary to hypercortisolism

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▼ AgainstLarge FDA's rejection letter found the efficacy evidence insufficient

FDA's complete response letter (effective 30 December 2025; corrected version signed 28 January 2026) says the evidence "is not sufficient to demonstrate the effectiveness of relacorilant for the proposed indication". GRACE "met its primary endpoint", but "the analysis was conducted in a highly enriched population": of 102 patients with hypertension at baseline, 40 (39%) left during the open-label phase and only 46 (45%) entered the randomized-withdrawal phase, so the result "likely overestimates the treatment effect" in the intended population. GRADIENT, the parallel-group placebo-controlled trial, "did not meet its primary efficacy endpoint": 24-hour systolic pressure fell 5.8 mm Hg on relacorilant and 5 mm Hg on placebo (difference -0.85 mm Hg; 95% CI -6.7 to 4.9; p=0.77). Corcept's post hoc analysis in 33 patients with Cushing's syndrome (difference -10.4 mm Hg; nominal p=0.03) included only 8 of 16 and 13 of 17 patients; FDA's own analysis with a different method for missing data gave -4.9 mm Hg (95% CI -15.3 to 5.6; nominal p=0.36). The published GRACE paper shows how small the pivotal comparison was: 21 patients on relacorilant and 22 on placebo (odds ratio 0.17; 95% CI 0.04-0.77; p=0.022). FDA added that before submission it had told Corcept "on several occasions" of its concerns and "to expect significant review issues".

Source: FDA Corrected Complete Response Letter, NDA 219398, signed 2026-01-28: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf; Pivonello et al., Lancet Diabetes Endocrinol 2026;14(4):291-304: https://pubmed.ncbi.nlm.nih.gov/41730814/
02▼ AgainstLarge The resubmission adds analyses, not the new clinical data FDA asked for

Under "Path forward" the letter says: "you will need to provide new clinical data to demonstrate that relacorilant treatment results in a clinically meaningful" effect (the endpoint is redacted), and offers a meeting "to discuss a feasible controlled clinical trial design using a novel endpoint such as a composite of signs and symptoms". FDA also reviewed the exploratory findings on body weight and blood glucose and was "not persuaded that such benefits were observed". The resubmission of 17 June 2026, in Corcept's words, "includes additional analyses of data included in the original NDA submission" and rests on the same studies: GRACE, GRADIENT, the long-term extension study and earlier trials. ClinicalTrials.gov lists no new controlled trial of relacorilant in Cushing's syndrome. What the analyses are, and what they show, is not public. Efficacy problems are historically the hardest to cure: in FDA's own study of new molecular entities first submitted in 2000-2012, efficacy deficiencies were present in 61 of the 80 applications never approved, against 28 of the 71 approved after resubmission. The 76% base rate describes first-time applications.

Source: FDA Corrected Complete Response Letter, NDA 219398: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf; Corcept 8-K exhibit 99.1, 2026-06-17: https://www.sec.gov/Archives/edgar/data/1088856/000119312526274258/d159941dex991.htm; ClinicalTrials.gov, studies of relacorilant: https://clinicaltrials.gov/search?intr=relacorilant; Sacks et al., JAMA 2014;311(4):378-84: https://pubmed.ncbi.nlm.nih.gov/24449316/
03▲ SupportsLarge After the rejection, FDA itself asked for further analyses and started a new review

Corcept met FDA in April 2026. Its quarterly report says: "In April 2026, the FDA asked us to conduct additional analyses of the data included in our NDA. Based on the outcome of those analyses, we resubmitted our NDA to the FDA on June 17, 2026. The FDA has assigned a Prescription Drug User Fee Act target date of December 17, 2026 to complete its review." On 27 May the chief executive said the agency "has told us to expect" a goal date six months after submission, and on 29 July that "the FDA accepted our resubmission". Six months is FDA's goal for a Class 2 resubmission; Corcept has not used the term. In February Corcept had named three possible outcomes of the meeting: resubmission with additional analyses, a formal appeal, or a new study. The lightest of the three followed. FDA's letter had warned that "a partial response to this letter will not be processed as a resubmission", yet FDA started a review clock on a package without the new clinical data the letter called for. Limits: every account of the April request comes from Corcept, FDA has not commented on it in public, and accepting a resubmission for review is not a finding that it is adequate.

Source: Corcept 10-Q filed 2026-07-29: https://www.sec.gov/Archives/edgar/data/1088856/000162828026050613/cort-20260630.htm; Corcept press release, 2026-05-27: https://www.biospace.com/press-releases/corcept-to-resubmit-its-new-drug-application-for-relacorilant-as-a-treatment-for-patients-with-cushings-syndrome; Q1 2026 results call transcript, 2026-04-30: https://www.fool.com/earnings/call-transcripts/2026/05/04/corcept-cort-q1-2026-earnings-transcript/; Q2 2026 results call transcript, 2026-07-29: https://www.investing.com/news/transcripts/earnings-call-transcript-corcept-therapeutics-q2-2026-revenue-beat-lifts-stock-93CH-4821896; Q4 2025 results call transcript, 2026-02-24: https://www.fool.com/earnings/call-transcripts/2026/05/04/corcept-cort-q4-2025-earnings-transcript/; PDUFA performance goals FY2023-2027, section I.A.1: https://www.fda.gov/media/151712/download; FDA Corrected Complete Response Letter: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf
04▼ AgainstMedium A liver-injury signal with daily dosing

After its safety review FDA "concluded that relacorilant is associated with drug induced liver injury (DILI)". Among 303 people who received the drug, four cases were assessed as probable DILI; one patient's ALT reached 1952 U/L, "more than 50 times the upper limit of normal". None met Hy's law criteria. FDA wrote that more cases may occur with longer exposure after approval and that "we cannot conclude that relacorilant has a favorable benefit risk assessment for the proposed indication". It also recommended a proposal for "DILI risk mitigation strategies including appropriate labeling warnings, routine monitoring requirements, enhanced pharmacovigilance, and post-market evaluation", which suggests the risk could be handled in labeling once benefit is shown. Corcept disputes the finding: on 24 February 2026 its chief development officer said the company's assessment, confirmed by an external independent safety committee, was that the endocrinology programme had no cases of drug-induced liver injury. The label of Lifyorli, approved in March 2026 at 150 mg on three days around each chemotherapy infusion, has no liver-injury warning; treatment of Cushing's syndrome is daily and long-term (100 to 400 mg a day in GRACE).

Source: FDA Corrected Complete Response Letter, NDA 219398: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf; Q4 2025 results call transcript, 2026-02-24: https://www.fool.com/earnings/call-transcripts/2026/05/04/corcept-cort-q4-2025-earnings-transcript/; Lifyorli prescribing information: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fcebfb5-19d6-4f63-b852-999d68a13729; Pivonello et al. 2026: https://pubmed.ncbi.nlm.nih.gov/41730814/
05▲ SupportsSmall The pivotal trial met its planned endpoint and the mechanism is established

FDA's letter accepts that GRACE "met its primary endpoint": among patients whose blood pressure had responded, those switched to placebo lost control more often than those kept on relacorilant (proportion difference 34%; odds ratio 0.17; p=0.022). In GRADIENT (137 patients, double-blind, 22 weeks) the secondary endpoints favoured relacorilant with nominal significance, as reported by Corcept: body weight -3.9 kg against placebo (p=0.0001), fasting glucose -22.2 mg/dL (p=0.002) and HbA1c -0.3 percentage points (p=0.019). The letter itself says "relacorilant may have benefit for the broader indication", and since the resubmission Corcept describes the application as for "patients with Cushing's syndrome" where in December 2025 it said "hypertension secondary to hypercortisolism"; the indication actually proposed is not public. Relacorilant blocks the same receptor as mifepristone (Korlym), marketed for Cushing's syndrome since 2012, and has orphan designation. Against this, FDA was "not persuaded" by the weight and glucose findings, a failed trial's secondary endpoints carry little formal weight, and other approved medicines exist.

Source: FDA Corrected Complete Response Letter: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf; Pivonello et al. 2026: https://pubmed.ncbi.nlm.nih.gov/41730814/; Corcept 8-K exhibit 99.1, 2024-10-30: https://www.sec.gov/Archives/edgar/data/1088856/000162828024044318/exhibit991pressrelease10-3.htm; Corcept 8-K exhibit 99.1, 2025-12-31: https://www.sec.gov/Archives/edgar/data/1088856/000119312525338184/d50993dex991.htm; Corcept 8-K exhibit 99.1, 2026-06-17: https://www.sec.gov/Archives/edgar/data/1088856/000119312526274258/d159941dex991.htm
06▲ SupportsSmall FDA has reopened several rejected applications since its leadership changed

Commissioner Marty Makary's resignation was announced on 12 May 2026, and the acting head of FDA's drug centre (CDER), Tracy Beth Høeg, was dismissed days later. Michael Davis, the deputy director, who had earlier worked in the Office of New Drugs, became acting CDER director and was named permanent director on 8 September. BioPharma Dive reported that the acting leadership "largely reverted toward more traditional and flexible decision-making, reversing some positions on previously rejected or delayed drugs"; BioCentury counted at least seven therapies approved, revived or reopened since March 2026. Limits: the reversals named in press reports (Replimune's RP1, uniQure's Huntington's gene therapy, Atara's Ebvallo, Regenxbio's Hunter syndrome gene therapy) were at the biologics centre, not CDER; in June 2026 CDER still tied Disc Medicine's response to its rejection of bitopertin to results from an ongoing Phase 3 trial; and FDA's request to Corcept came in April, before these changes. No public record connects the two.

Source: STAT, 2026-05-12: https://www.statnews.com/2026/05/12/fda-commissioner-marty-makary-resigns-kyle-diamantas-acting/; pharmaphorum, 2026-05-18: https://pharmaphorum.com/news/after-refusing-resign-cder-head-hoeg-fired; BioPharma Dive, 2026-09-08: https://www.biopharmadive.com/news/fda-mikhail-davis-cber-cder-director-hhs/829886/; BioCentury, 2026-06-02: https://www.biocentury.com/article/659645/fda-reviving-drugs-derailed-under-makary-and-prasad; BioSpace, 2026-05-07: https://www.biospace.com/fda/fda-reverses-course-on-atara-pierre-fabres-twice-rejected-cell-therapy-after-prasads-exit; BioSpace, 2026-08-05: https://www.biospace.com/fda/chaotic-adcomms-threaten-to-derail-fdas-bid-to-renew-trust-after-makary-prasad; Disc Medicine release, 2026-06-09: https://www.globenewswire.com/news-release/2026/06/09/3308825/0/en/Disc-Medicine-Provides-Update-from-FDA-Type-A-Meeting-for-Bitopertin-in-Erythropoietic-Protoporphyria.html
07▲ SupportsSmall Product quality is not in question: the same capsules were approved in March 2026

FDA approved relacorilant 25 mg and 100 mg capsules as Lifyorli for ovarian cancer on 25 March 2026 (NDA 220641), three and a half months before its goal date of 11 July 2026. The Cushing's syndrome letter lists deficiencies only under "Clinical and Statistical"; it has no product-quality or facility section. Manufacturing problems are a frequent reason for FDA rejections, and that cause is largely absent here. The ovarian cancer approval does not bear on efficacy in Cushing's syndrome: it rested on a different trial in a different disease.

Source: FDA Drugs@FDA record for NDA 220641: https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA220641%22; Lifyorli prescribing information: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fcebfb5-19d6-4f63-b852-999d68a13729; Corcept 8-K exhibit 99.1, 2026-03-25: https://www.sec.gov/Archives/edgar/data/1088856/000119312526123543/d123475dex991.htm; FDA Corrected Complete Response Letter, NDA 219398: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf
08▼ AgainstSmall The company's confident account has diverged from FDA's before

Corcept says the analyses FDA requested had a "positive outcome", cites "the productive tenor of our discussions" and expects a decision by 17 December 2026. Its record in describing FDA's views is mixed. On 31 December 2025 it said FDA had acknowledged that GRADIENT "provided confirmatory evidence", and its quarterly report of 29 July 2026 still says so; the letter FDA published says GRADIENT "did not meet its primary efficacy endpoint". On 24 February 2026 its chief business officer said FDA had not told the company it "would face significant review issues"; the letter says FDA told it "to expect significant review issues". FDA reissued the letter on 28 January 2026 in response to a communication from Corcept, noting that the original "contained no errors". Since the resubmission there is no public record of labeling discussions, of an advisory committee meeting, or of any FDA comment on the new analyses. On 23 September 2026 Corcept announced that the president of its endocrinology division would retire on 1 October, 11 weeks before the goal date, and stay on as an adviser; his successor built the Lifyorli sales organisation. The announcement does not mention relacorilant.

Source: Corcept press release, 2026-05-27: https://www.biospace.com/press-releases/corcept-to-resubmit-its-new-drug-application-for-relacorilant-as-a-treatment-for-patients-with-cushings-syndrome; Corcept 8-K exhibit 99.1, 2026-07-29: https://www.sec.gov/Archives/edgar/data/1088856/000162828026050607/cort072926ex991pressrelease.htm; Corcept 8-K exhibit 99.1, 2025-12-31: https://www.sec.gov/Archives/edgar/data/1088856/000119312525338184/d50993dex991.htm; Corcept 10-Q filed 2026-07-29: https://www.sec.gov/Archives/edgar/data/1088856/000162828026050613/cort-20260630.htm; Q4 2025 results call transcript, 2026-02-24: https://www.fool.com/earnings/call-transcripts/2026/05/04/corcept-cort-q4-2025-earnings-transcript/; FDA Corrected Complete Response Letter: https://download.open.fda.gov/crl/CRL_NDA219398_20260128.pdf; BioSpace, 2026-02-02: https://www.biospace.com/fda/fda-warned-corcept-of-significant-review-issues-for-rejected-drug-in-early-meetings; FDA advisory committee page, 2026 meeting materials: https://www.fda.gov/advisory-committees/endocrinologic-and-metabolic-drugs-advisory-committee/2026-meeting-materials-endocrinologic-and-metabolic-drugs-advisory-committee; Corcept 8-K and exhibit 99.1, 2026-09-23: https://www.sec.gov/Archives/edgar/data/1088856/000119312526398561/d148256d8k.htm; https://www.sec.gov/Archives/edgar/data/1088856/000119312526398561/d148256dex991.htm

What would change this forecast

01
Up: Corcept discloses labeling discussions with FDA, or FDA requests about liver-monitoring language or post-marketing studies.
02
Up: it becomes public what the requested analyses were and that FDA defined them in advance as a basis for approval; or CDER approves another drug it had rejected on efficacy grounds after re-analysis of existing trials.
03
Down: Corcept registers or announces a new controlled trial of relacorilant in Cushing's syndrome, or says FDA has asked for additional clinical data.
04
Down: Corcept's next quarterly report, expected in early November 2026, adds cautionary wording about the review or leaves relacorilant out of its near-term growth statements.
05
Down: new cases of serious liver injury are reported in the long-term extension study or with Lifyorli, or a liver warning is added to the Lifyorli label.
06
Void rather than no: Corcept withdraws the application before FDA acts.

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Low

Manufacturing and inspection risk

Low

Relacorilant 25 mg and 100 mg soft gelatin capsules were approved as Lifyorli on 25 March 2026 (NDA 220641), so the drug substance and the capsule manufacture passed FDA review this year. FDA's complete response letter for the Cushing's syndrome application lists deficiencies only under "Clinical and Statistical" and has no product-quality or facility section. Corcept has supplied Korlym commercially since 2012. What cannot be judged: Corcept does not name its contract manufacturers in its SEC filings, so their inspection records cannot be checked; daily dosing for Cushing's syndrome (100 to 400 mg in GRACE) needs different packaging from the co-packaged oncology dose cards; and there is no public record of any inspection tied to this resubmission.

Record · version 1

Written on 2026-10-05, 73 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-05 08:21 UTC 40% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

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Verify it yourself

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Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-12-15. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.