Crinetics presents Phase 2 atumelnant CAH data at ENDO 2026
Crinetics Pharmaceuticals has presented full Phase 2 results for its investigational ACTH receptor antagonist atumelnant in adults with classic congenital adrenal hyperplasia (CAH), reporting that the drug enabled participants to reduce glucocorticoid supplementation to physiologically normal levels while sustaining meaningful androgen suppression.
The data, delivered in an oral session at the Endocrine Society's annual ENDO 2026 meeting in San Diego, covered Cohort 4 of the open-label TouCAHn trial, in which participants received 80 mg of atumelnant once daily in the morning. Starting at week two, glucocorticoid doses were stepped down by 5 to 10 mg hydrocortisone equivalents regardless of androstenedione (A4) readings, with a target of less than 11 mg/m² per day.
Cohort 4 results
At week 12, mean morning serum A4 had fallen by 67% from baseline. Seven of eight participants who completed the full 12 weeks achieved a physiologic daily glucocorticoid dose. Reductions in the androgen markers 11-OHA4 and 11-KT were also rapid and sustained, with mean changes from baseline of minus 64% and minus 56% respectively. The company reported no treatment-related severe or serious adverse events across any cohort or dose level to date.
Crinetics also presented new data from its Phase 1b/2a study of atumelnant in ACTH-dependent Cushing's syndrome (ADCS), a collaboration with the National Institutes of Health. In a six-patient cohort receiving 40 mg once daily over ten days, the drug rapidly reduced early morning serum cortisol in all participants and brought urinary free cortisol to within the normal range in three of the six by the end of the dosing period. Most adverse events were mild to moderate and consistent with adrenal insufficiency symptoms, the majority resolving with glucocorticoid replacement.
Alan Krasner, chief endocrinologist at Crinetics, said the data supported advancing atumelnant into late-phase development, describing it as potentially "a uniquely effective and simple to use oral therapy for many patients who need new options." Umasuthan Srirangalingam, consultant physician at University College London Hospitals NHS Foundation Trust and a TouCAHn investigator, highlighted that glucocorticoid dose reduction did not blunt the androgen-lowering effect, calling the finding clinically meaningful ahead of adult and paediatric Phase 3 trials that are already enrolling.
Market context and competitive landscape
CAH caused by 21-hydroxylase deficiency is a lifelong condition with no approved targeted therapy; current standard of care relies on supraphysiologic glucocorticoid dosing to suppress excess adrenal androgens, a regimen that carries significant long-term metabolic and cardiovascular risk. The ability to reduce glucocorticoid burden while maintaining androgen control is a key efficacy benchmark the field has long sought.
Atumelnant is not the only programme pursuing this unmet need. Neurocrine Biosciences received FDA approval for crinecerfont, a CRF1 receptor antagonist, in late 2024 for adult and paediatric CAH, establishing the first approved non-steroid adjunct therapy in the indication. Crinetics is positioning atumelnant at the upstream ACTH receptor rather than the CRF1 pathway, a mechanistic distinction it argues offers more direct suppression of adrenal stimulation. Whether that translates to a differentiated clinical profile will hinge on head-to-head or cross-trial comparisons in Phase 3, where the CALM-CAH study is currently enrolling. Regulatory interactions to support a filing timeline have not yet been disclosed by the company.
Crinetics already has one approved product on the market, PALSONIFY (paltusotine), cleared by the FDA and EMA for acromegaly, giving the company a commercial infrastructure and endocrinology relationships that could support atumelnant's eventual launch.