Relacorilant: when evidence meets the established evidence bar

This blog post is the third in our series about the Complete Response Letters (CRLs) that the U.S. Food and Drug Administration (FDA) issued to Sanofi for tolebrutinib to treat non-relapsing secondary progressive multiple sclerosis (nrSP-MS) on December 23, 2025, and to Corcept Therapeutics for relacorilant to treat Cushing syndrome on December 30, 2025. Both drugs are included in the Clarivate “Drugs to Watch 2026” report, and these decisions came after the report was finalized.

In the CRL for relacorilant, the FDA concluded it “could not arrive at a favorable benefit-risk assessment without Corcept providing additional evidence of effectiveness.” It did not cite concerns about the drug’s efficacy or safety data per se, but rather indicated the agency needs more evidence to definitively establish that benefits outweigh risks.

The clinical context

Relacorilant, a selective glucocorticoid receptor antagonist (SGRA), blocks cortisol signaling without binding to progesterone receptors — a key differentiator from existing therapies. In a heterogeneous Cushing syndrome population, the phase 3 GRACE trial met its primary endpoint, demonstrating significant improvements in systolic and diastolic blood pressure (mean changes of -7.9 and -5.1 mm Hg, respectively, P<.0001 for both) at 22 weeks in patients with hypertension.

The GRADIENT trial, conducted with patients with hypercortisolism caused by adrenal adenomas or hyperplasia, which represented a narrower patient subgroup, showed similar blood pressure control benefits (treatment difference of -6.6 mm Hg with relacorilant vs -2.1 mm Hg with placebo at week 22). Although the reduction with relacorilant was statistically and clinically significant, the difference between relacorilant and placebo was not.

The market impact

Although relatively small, the Cushing syndrome therapeutics market represents a substantial opportunity. Valued at $383-386m in 2025, it’s projected to grow at a CAGR of 5.64% through 2030. Corcept had projected relacorilant could capture $3bn to $5bn annually within 3-5 years post-approval across its indications, implying a potential 50-85% market share in hypercortisolism.

Relacorilant’s competitive positioning centers on its differentiated safety profile. Unlike mifepristone (Korlym®, also from Corcept), relacorilant avoids progesterone receptor binding, potentially cutting gynecologic adverse events by 70%. It also doesn’t cause adrenal insufficiency or hypokalemia seen with other treatments.

Following the CRL announcement, Corcept’s stock declined 50.4%, reflecting investor response and revised assessments of development risk.

The silver lining: ovarian cancer pathway

Relacorilant’s regulatory journey extends beyond Cushing syndrome. The NDA for platinum-resistant ovarian cancer has a PDUFA decision date of July 11, 2026. Positive phase 3 ROSELLA trial results supported the application: relacorilant plus nab-paclitaxel demonstrated superior progression-free survival (6.5 vs 5.5 months) and overall survival (16.0 vs 11.5 months) without greater toxicity than with nab-paclitaxel alone.

Additionally, the CRL pertains only to Cushing syndrome, does not indicate a blanket efficacy/safety concern and is independent from the ovarian cancer submission.

The unmet need is significant, with current therapies for platinum-resistant ovarian cancer offering limited durability, and the second- and third-line platinum-resistant ovarian cancer drugs market is projected to reach $2.3bn by 2034, representing 39% of major-market sales.

How Clarivate can help address regulatory challenges

Cortellis Regulatory Intelligence + AI-powered Regulatory Assistant

Cortellis Regulatory Intelligence delivers critical regulatory intelligence combining broad and deep insights with subject matter expertise, now enhanced by AI-powered capabilities through the Regulatory Assistant. Corcept faces a nuanced regulatory challenge: the FDA acknowledged their data but wants more. The Regulatory Assistant can help Corcept understand exactly what “additional evidence” means in context.

Understand FDA’s evidence bar and successful precedents

• Querying precedents for approval pathways: To understand similar situations and successful resolution strategies, Regulatory Assistant queries could include “Show successful resubmissions after ‘insufficient evidence’ CRLs in rare endocrine diseases” or “Analyze FDA evidence standards for benefit-risk in small patient populations.”
• Evidence standards comparison: Corcept could analyze comparative assessments of regulatory strategies across jurisdictions to understand whether EMA’s evidence standards for hypercortisolism differ from FDA’s, informing both their EU submission strategy and potential arguments for FDA resubmission.
• Accelerated pathway analysis: The platform can help explore whether additional data from the pending ovarian cancer approval (PDUFA date: July 11, 2026) could support the Cushing resubmission, examining precedents where multi-indication data strengthened benefit-risk arguments.

DRG Fusion

DRG Fusion is powered by uniquely connected real-world data and an AI-driven experience that empower disease analysis from any angle.

Generate supportive effectiveness and safety evidence from real-world sources

• Natural history comparators: DRG Fusion’s integrated claims data can characterize real-world progression of untreated or inadequately treated Cushing syndrome, providing natural history comparisons that contextualize trial outcomes and demonstrate clinical meaningfulness.
• Mifepristone real-world effectiveness: Corcept’s first drug, mifepristone (Korlym), offers real-world evidence for effectiveness patterns, durability of response and long-term safety in real-world patients with Cushing syndrome, potentially supporting a class effect argument for SGRAs or demonstrating relacorilant’s differentiated profile.
• Patient journey analysis: The platform’s patient journey analysis modules can map the Cushing syndrome patient experience, demonstrating treatment gaps, unmet needs and the clinical contexts where relacorilant would provide meaningful benefit to strengthen the clinical meaningfulness argument.
• Long-term safety validation: Real-world safety data can supplement trial evidence, demonstrating acceptable long-term tolerability profiles that strengthen benefit-risk assessment.

Cortellis Clinical Trials Intelligence

Cortellis Clinical Trials Intelligence offers insights into clinical trial progression, competitor strategies and protocol design optimization, which could help optimize additional prospective studies if they’re needed.

Design targeted additional studies (if needed) with highest success probability

• Endpoint selection: For hypercortisolism, Corcept could benchmark which endpoints (blood pressure control, glucose metabolism, quality of life, weight reduction) have proven most persuasive to regulators in rare endocrine diseases.
• Site selection optimization: Across more than 277k sites in 200 countries, Corcept can identify endocrinology centers with proven Cushing’s expertise and patient access, a critical consideration for a rare disease.
• Protocol feasibility: The platform can perform thorough trial feasibility analysis by understanding successful protocols, sites and patient segments and evaluating extensive site intel integrating epidemiology data, site availability and recruitment.
• Stratification strategies: Analysis of successful patient stratification approaches in rare endocrine disease trials can optimize protocol designs for demonstrating benefit across heterogeneous patient populations.

Epidemiology Intelligence

Epidemiology Intelligence helps size the market and understand patient populations using a combination of incidence and prevalence literature review across more than 1000 diseases and procedures.

Define Cushing’s subpopulations with the clearest demonstrated benefit

• Characterizing Cushing’s syndrome subpopulations: The platform enables definition by etiology (pituitary, adrenal, ectopic), disease severity and comorbidity profiles.
• Quantifying addressable patient populations: Targeted regulatory and commercial strategies can be stress-tested.
• Supporting precision-targeting arguments: Which strategies demonstrate meaningful clinical benefit in well-defined segments can be determined.

Our previous blog post, Tolebrutinib: when safety concerns override efficacy signals, discussed the impact of the CRL for tolebrutinib and how trusted intelligence could help address the FDA’s concerns. Our next and final post in this series will look at some takeaways for Sanofi and Corcept and how companies can chart a path forward from a CRL.

Learn more about our 2026 Drugs to Watch , and you can read about how Clarivate is using AI tools to empower its clients to make better decisions faster.

Biopharma Biotech Clinical trials Commercialization FDA Market Access Pharma Real-World Data Regulatory Safety U.S.

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