Crinetics Pharmaceuticals Inc. (NASDAQ:CRNX) released encouraging topline data from the fourth cohort in its Phase 2 clinical trial assessing atumelnant for treating congenital adrenal hyperplasia (CAH) and adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome. CAH is a hereditary condition impairing adrenal gland function, resulting in deficient production of key hormones, including cortisol, aldosterone, and androgens.
Detailed Outcomes from the Fourth Cohort
In the subset of eight patients completing this fourth cohort, treatment with atumelnant led to an immediate and sustained decrease in androstenedione (A4) levels across the board. Notably, seven of these patients maintained these lowered A4 concentrations even after tapering glucocorticoid (GC) therapy down to physiological replacement thresholds. At a dosing regimen of 80 mg, atumelnant achieved an average reduction of 67% in serum androstenedione levels. Moreover, 88% of participants who completed 12 weeks on therapy successfully diminished their GC dosage to physiologic levels.
The safety data from this cohort showcased a favorable tolerability profile, with no serious adverse events reported. None of the participants discontinued treatment due to adverse effects, and there were no instances of severe adverse events related to the drug or hepatic transaminase elevations.
Insights from the Open-Label Extension of the TouCAHn Trial
Interim data from the open-label extension (OLE) phase of the TouCAHn trial further reinforce the phase 2 findings. A snapshot analysis, albeit with limited source data verification, involved seven patients who completed at least 13 weeks of follow-up. The results indicated consistent reductions in serum A4 and GC doses comparable to those observed in the fourth cohort.
Throughout this extension phase, comprising 25 enrolled participants with seven patients surpassing 20 weeks of therapy, no serious or treatment-related severe adverse events have surfaced. Hepatic transaminase elevations have also not been reported to date. Collectively, the accumulating safety data reflect over 750 weeks of cumulative exposure in adults with CAH, underscoring atumelnant’s well-tolerated nature.
Recent Regulatory and Commercial Progress
In an important commercial development, the U.S. Food and Drug Administration (FDA) granted approval for Crinetics’s Palsonify (paltusotine) in September 2025. This oral agent is indicated as a first-line therapy for adults with acromegaly who have exhibited inadequate responses to surgery or for whom surgery is not a viable option. The approval facilitated revenue recognition exceeding $5 million for Crinetics in the fourth quarter of 2025.
Competitive and Regulatory Context in Related Therapeutics
Separately, regulatory setbacks have afflicted other firms in the therapeutic area. In December 2025, the FDA rejected Corcept Therapeutics Incorporated’s New Drug Application for relacorilant in treating hypertension secondary to hypercortisolism due to insufficient evidence supporting its effectiveness.
In contrast, the FDA approved Neurocrine Biosciences, Inc.’s Crenessity (crinecerfont) in December 2024 as an adjunct treatment to glucocorticoid therapy for controlling androgens in both adult and pediatric patients with classic CAH as young as four years old.
Market Response and Stock Performance
Crinetics Pharmaceuticals shares responded positively to these developments, rising 13.19% to close at $52.89 during Monday trading, approaching the stock’s 52-week peak of $53.55. This uptick reflects investor confidence surrounding the clinical progress and commercial momentum of the company’s product portfolio.
Key Points
- Atumelnant treatment in Phase 2 trial resulted in a 67% mean reduction in serum androstenedione among CAH patients, supporting hormone control.
- Majority of patients were able to reduce glucocorticoid doses to physiological replacement levels without compromising hormonal management.
- Safety profile remains favorable with no serious treatment-related adverse events or hepatic enzyme elevations reported.
- The FDA approved Palsonify in 2025 as a novel oral therapy for acromegaly, contributing to recent revenue gains for Crinetics.
Risks and Uncertainties
- Phase 2 results, though promising, require confirmation in larger or later-stage trials to establish long-term efficacy and safety.
- Ongoing regulatory processes and market acceptance of new therapies can affect future commercial success.
- Competitive landscape remains dynamic, with other companies pursuing treatment options for CAH and related endocrine disorders.
- Safety data, while currently favorable, is based on relatively limited patient exposure and longer-term monitoring is necessary.