Corcept Therapeutics (NASDAQ: CORT) plunges as FDA rejects relacorilant for Cushing’s-related hypertension therapy

Corcept Therapeutics Incorporated (NASDAQ: CORT) announced on December 31, 2025, that the United States Food and Drug Administration (FDA) issued a Complete Response Letter declining approval of its experimental drug relacorilant for the treatment of hypertension associated with endogenous Cushing’s syndrome. The regulatory rejection dealt a significant blow to Corcept Therapeutics’ near-term commercial strategy, sending the company’s shares down more than 35 percent in pre-market trading.

The decision reflects a broader shift in regulatory scrutiny for rare endocrine therapies. While Corcept Therapeutics had positioned relacorilant as a follow-on to its approved product Korlym, the FDA cited insufficient evidence to support a favorable benefit-risk profile, forcing a strategic reassessment and likely delaying the company’s path to revenue diversification.

Why did the FDA reject relacorilant despite positive results in pivotal trials like GRACE?

Corcept Therapeutics’ new drug application for relacorilant was backed by two core clinical studies: the Phase 3 GRACE trial and the GRADIENT trial. The GRACE study met its primary endpoint by demonstrating statistically significant improvement in blood pressure and related symptoms in patients with endogenous hypercortisolism who were not eligible for surgery. GRADIENT, while not powered for the same endpoints, was designed to offer supportive evidence in patients with adrenal adenomas and subclinical disease.

Despite these outcomes, the FDA concluded that the totality of data did not justify approval under the current application. The agency’s primary concern appears to center on variability in treatment response across patient subgroups and questions regarding the consistency of benefit when stratified by baseline severity, comorbidity, and duration of disease.

Importantly, the Complete Response Letter did not identify safety concerns, nor did it request new preclinical studies. That suggests the FDA’s reservations are grounded in efficacy interpretation and statistical confidence, rather than in toxicity, off-target effects, or manufacturing issues.

This nuanced rejection has frustrated investors and clinical observers alike, as it highlights the rising regulatory bar for demonstrating clinical benefit in small populations where placebo-controlled trials are already difficult to execute and ethically complex.

How significant was relacorilant in Corcept Therapeutics’ growth trajectory and investor narrative?

Relacorilant was not just another pipeline candidate. It was the most advanced product in Corcept Therapeutics’ post-Korlym portfolio and central to its near-term investor story. Korlym, approved for Cushing’s syndrome in 2012, has reached commercial maturity. Relacorilant was intended to expand the company’s addressable market, reduce Korlym’s safety liabilities by avoiding progesterone receptor activity, and unlock growth in oncology and metabolic indications.

By targeting hypertension as a clinically measurable endpoint, Corcept Therapeutics had hoped to secure a broad indication under the hypercortisolism umbrella. Approval would have validated the strategy of modulating the glucocorticoid receptor with higher receptor selectivity. It would also have opened doors for cross-label leverage into related conditions like diabetes mellitus and depression associated with cortisol excess.

With this setback, the company faces not only a delay in new revenue generation but a deeper challenge in defending its valuation. The stock’s steep decline reflects both the lost potential of relacorilant’s approval and the broader concern that Corcept Therapeutics’ pipeline may not be diverse enough to withstand such binary risks.

What are the realistic regulatory next steps available to Corcept Therapeutics?

Corcept Therapeutics stated that it intends to meet with the FDA to better understand the agency’s concerns and explore options for resubmission. Several possibilities exist, depending on the level of divergence between FDA reviewers and the company’s interpretation of the trial data.

One path could involve providing additional stratified analyses or responder-enrichment strategies using existing trial datasets. If the FDA finds such reanalysis compelling, a Class 1 or Class 2 resubmission could follow within six to ten months. Alternatively, the agency may recommend a confirmatory trial, likely focused on a narrower patient population with more severe or uncontrolled hypertension.

A more complex but potentially faster path would be a restricted label submission based on subsets from GRACE, where efficacy was strongest. However, that would limit commercial upside and raise access and pricing challenges.

The key signal will be the tone of the upcoming FDA meeting. If the agency expresses openness to collaborative data refinement, relacorilant may still receive approval with a modified label. If not, a multi-year delay looms, during which time competitors may advance their own assets targeting the same receptor axis or endocrine pathways.

Can Corcept Therapeutics salvage relacorilant’s narrative through other indications?

Although hypercortisolism was the lead indication, relacorilant is also under investigation in oncology, particularly in platinum-resistant ovarian cancer. Corcept Therapeutics is running a Phase 3 trial assessing relacorilant in combination with nab-paclitaxel, aiming to improve progression-free survival by neutralizing cortisol-mediated chemotherapy resistance.

This oncology program represents a high-reward but high-risk avenue. Success in that setting could substantially revalue the asset and justify a pivot in narrative from endocrine disorders to solid tumor therapeutics. However, the oncology timeline extends into late 2026 and beyond, with significant capital outlays expected.

Corcept Therapeutics also has early-stage programs in glioblastoma and metabolic liver disease, but none are positioned to deliver near-term regulatory decisions or commercial launches. Without relacorilant’s approval in Cushing’s-related hypertension, these programs now bear greater weight in justifying long-term investment.

How has investor sentiment and institutional positioning shifted post-rejection?

The rejection catalyzed a sharp reevaluation of Corcept Therapeutics’ risk profile among institutional investors. Prior to the FDA decision, the company had traded with an implicit approval probability priced in, given the Phase 3 success and lack of major safety concerns.

In the days following the announcement, several analysts downgraded the stock, slashed price targets, and flagged elevated uncertainty around management’s ability to mitigate clinical and regulatory risk. Sentiment data suggests a sharp rise in bearish options activity, increased short interest, and reduced institutional net buying.

At the same time, some hedge funds and event-driven investors have taken the opportunity to initiate positions at lower valuations, citing Corcept Therapeutics’ strong gross margins, minimal debt, and potential upside from future relacorilant readouts in oncology. The long-short bifurcation of sentiment reflects the binary nature of the FDA’s decision and the path-dependence of the company’s recovery.

What broader lessons does this rejection signal for the endocrine and orphan drug sectors?

Corcept Therapeutics’ experience highlights a critical regulatory shift. The FDA is demanding higher statistical confidence and subgroup consistency even in rare endocrine diseases, where historical approval standards were more flexible due to the small patient populations and urgent unmet need.

Other companies developing glucocorticoid receptor modulators, cortisol pathway inhibitors, or enzyme-based therapies for Cushing’s syndrome and adrenal disorders may now face elevated expectations on trial design, endpoint selection, and biomarker integration.

The rejection also underscores the importance of regulatory science strategy. Biotechs must anticipate not just top-line efficacy but regulatory interpretability, particularly when operating in mechanistically complex diseases where symptom heterogeneity can obscure benefit.

For large-cap incumbents, the news creates a temporary white space in the market. Players with access to legacy cortisol-modulating compounds, or those willing to revisit older mechanisms of action with improved safety profiles, may consider accelerated entry or reentry into the space.

Could Corcept Therapeutics pursue partnerships or M&A to rebuild pipeline momentum?

Given the delay in relacorilant’s approval and the weight of uncertainty in its timeline, Corcept Therapeutics may explore partnerships or licensing to diversify pipeline risk. Strategic collaboration around relacorilant’s oncology applications or out-licensing of non-core assets could bring near-term capital and de-risk clinical execution.

Additionally, Corcept Therapeutics’ balance sheet and modest burn rate may position it as an acquirer of early-stage assets in adjacent endocrine or neuropsychiatric indications. Whether management opts for in-licensing, merger activity, or internal acceleration will depend on the clarity of FDA feedback and the strength of investor pressure to diversify.

If no commercial-stage asset is added in the near term, and if relacorilant’s timeline stretches beyond 2027, Corcept Therapeutics risks losing relevance in a market where biotech investors are increasingly impatient with binary single-asset plays.

Key takeaways on what the FDA rejection of relacorilant means for Corcept Therapeutics and the sector

• The U.S. Food and Drug Administration rejected Corcept’s NDA for relacorilant in hypercortisolism, citing insufficient benefit-risk evidence.

• This outcome halts the company’s most advanced commercial program and has triggered a 35 percent drop in share price.

• Corcept’s GRACE and GRADIENT trial data, while positive, did not meet the regulatory bar for approval in this rare endocrine indication.

• The company’s pipeline is now heavily reliant on oncology trials for relacorilant, which are still years from potential approval.

• Institutional sentiment has turned negative, with downgrades and volatility reflecting deep concern over strategy execution.

• Corcept will need to engage with the FDA on revised data strategies, including subgroup analysis or new trials.

• The rejection raises the bar for all glucocorticoid receptor modulators targeting rare hormonal disorders.

• Peer companies may need to revisit trial designs and statistical powering assumptions in light of this development.