Congenital adrenal hyperplasia (CAH) is a group of inherited enzyme deficiencies in adrenal-cortex steroid biosynthesis that produces a characteristic pattern of cortisol deficiency plus over-production of androgens. About 95% of classic-CAH cases are caused by 21-hydroxylase deficiency; roughly 5% are caused by 11β-hydroxylase deficiency, which adds accumulation of 11-deoxycortisol and 11-deoxycorticosterone to the cortisol-deficiency picture. Patients have historically been managed with chronic supraphysiologic glucocorticoid dosing to suppress excess ACTH-driven androgen production, at the cost of long-term metabolic and bone consequences.
The field is now being reshaped by two competing CRH/ACTH-pathway approaches. Neurocrine Biosciences' CRENESSITY (crinecerfont) is a small-molecule CRF1 receptor antagonist that dampens the upstream CRH-ACTH peptide signaling axis. The Phase 3 CAHtalyst Adult two-year data presented at AACE 2026 showed a 38% sustained glucocorticoid dose reduction; pediatric two-year data at ENDO 2026 added durable hormone control plus improved weight, insulin resistance, and bone-age outcomes. The first retrospective 11β-hydroxylase case series, presented at ENDO 2026 in June 2026, supports further exploration of crinecerfont in that subtype. Crinetics Pharmaceuticals' atumelnant (CRN04894), a small-molecule ACTH receptor antagonist that acts one step downstream of CRH, posted full Phase 2 results at ENDO 2026 showing rapid, sustained reductions in androstenedione and 17-hydroxyprogesterone with glucocorticoid dose reductions.
Stories here cover CAH trial readouts and the CRH-ACTH peptide-pathway competitive set. See [[crenessity]], [[atumelnant]], and [[cushings-syndrome]] for adjacent threads.
Crinetics Pharmaceuticals (Nasdaq: CRNX) presented on June 14 full results from its 12-week Phase 2 trial of atumelnant (CRN04894) in adults with classic congenital adrenal hyperplasia (CAH), the company's investigational once-daily oral ACTH receptor antagonist. The data showed rapid, substantial, and sustained statistically significant reductions in CAH disease biomarkers including androstenedione and 17-hydroxyprogesterone, with patients able to reduce glucocorticoid doses while maintaining androgen control. A separate Phase 1b/2a interim analysis in ACTH-dependent Cushing's syndrome showed that atumelnant rapidly lowered early-morning cortisol and normalized urinary free cortisol even at lower doses. Both programs are advancing toward Phase 3.
Neurocrine Biosciences (Nasdaq: NBIX) presented two-year data from CAHtalyst Pediatric showing durable hormone control, reduced glucocorticoid exposure, and improved growth measures in pediatric patients with classic congenital adrenal hyperplasia (CAH), with weight, insulin resistance, and bone-age outcomes also improved at year 2. Separately, Neurocrine announced the first retrospective case series of CRENESSITY (crinecerfont) in patients with classic CAH due to 11β-hydroxylase deficiency, the second-most-common form of CAH after 21-hydroxylase deficiency, accounting for roughly 5% of cases. The 11β-OHD subtype was not previously studied in the crinecerfont trials and is characterized by cortisol deficiency plus excess adrenal androgens and accumulation of 11-deoxycortisol and 11-deoxycorticosterone. Crinecerfont is a small-molecule CRF1 receptor antagonist that dampens the CRH-ACTH peptide signaling axis.
Neurocrine Biosciences announced April 22 two-year data from the Phase 3 CAHtalyst Adult study at AACE 2026 in Las Vegas. CRENESSITY (crinecerfont), a CRF1 receptor antagonist that dampens the CRF-ACTH peptide signaling axis, achieved sustained glucocorticoid dose reductions in adults with classic congenital adrenal hyperplasia: mean daily GC dose decreased from 17.6 to 10.6 mg/m²/day HCe (−38%), and approximately 69% of patients achieved GC doses within the physiologic range while maintaining androgen control. No new safety signals emerged.