OR07-04 Crinecerfont Allows for More Physiologic Glucocorticoid Treatment With Reduction of Androstenedione to a Normal Range in Adults With Classic Congenital Adrenal Hyperplasia: Post Hoc Analyses of the CAHtalyst™ Adult Study
Bibliographic record
Abstract
Abstract Disclosure: O. Hamidi: Advisory board member for Neurocrine Biosciences,Corcept Therapeutics, Recordati Rare Diseases, Crinetics Pharmaceuticals, Inc, Camurus, Xeris Pharmaceuticals, Inc, Educational speaking engagement with Recordati Rare Diseases. S.A. Imran: None. A.M. Isidori: Research funding from Corcept, Recordati Rare Diseases Pharma, Pzifer, Principal Investigator for Neurocrine Biosciences, Inc, Crinetics Pharma. H. Falhammar: None. N. Reisch: Consulted for Neurocrine Biosciences, Inc., Spruce Biosciences, H Lundbeck A/S, Crinetics Pharmaceuticals and Diurnal Limited. P. Rodien: None. R.H. Farber: Full-time employee of Neurocrine Biosciences, Inc. J. Sturgeon: Full-time employee of Neurocrine Biosciences, Inc. V.H. Lin: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc.. Background: Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class medication that is FDA-approved as an adjunct to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In two phase 3 trials, crinecerfont significantly reduced androstenedione (A4), enabling subsequent GC dose reductions in pediatric and adult patients with classic CAH. Objective: To analyze changes in GC doses in conjunction with A4 levels in CAHtalyst™ Adult (NCT04490915). Methods: Adults with CAH were randomized 2:1 to 24 weeks of double-blind treatment with crinecerfont (100 mg BID) or placebo. GC doses were kept stable for the first 4 weeks to measure the impact on androgens, followed by a planned GC down-titration over 8 weeks to achieve a target dose of 8-10 mg/m2/d in hydrocortisone equivalents (HCe). GC doses were then adjusted as needed over 12 weeks to maintain or improve A4 relative to baseline (BL). Achievement of a daily GC dose ≤11 mg/m2/d (protocol-defined “physiologic” range) while A4 was maintained/improved was assessed at Wk24 (key secondary endpoint). Since A4 could be higher than the upper limit of normal (>ULN) at BL (thus possibly elevated at Wk24 despite being maintained), a post hoc quadrant analysis was conducted based on GC dose and A4 normal range, with participants categorized at BL and Wk24 by GC dose (≤11 mg/m2/d or >11 mg/m2/d [“supraphysiologic” range]) and A4 (≤ULN or >ULN). Results: All participants were taking supraphysiologic GC doses at BL per study inclusion criteria (GC >13 mg/m2/d HCe). At Wk24, a higher percentage of participants achieved GC ≤11 mg/m2/d while maintaining/improving A4 with crinecerfont (63% [74/118] vs 18% [10/57] for placebo, P<0.0001). In the post hoc quadrant analysis, 50% had A4 >ULN at BL: crinecerfont 51% (60/118); placebo 49% (28/57). At Wk24, 82% (97/118) of crinecerfont-treated participants achieved GC ≤11 mg/m2/d regardless of A4 level; of these, 53% (51/97) had A4 ≤ULN. With placebo, 37% (21/57) were taking GC ≤11 mg/m2/d at Wk24; of these, 43% (9/21) had A4 ≤ULN. Moreover, 49% (28/57) of placebo-treated participants had A4 >ULN despite supraphysiologic GC dosing vs 11% (13/118) with crinecerfont. Conclusion: In CAHtalyst Adult, 63% of participants taking crinecerfont achieved a physiologic GC dose (≤11 mg/m2/d HCe) at Wk24 while maintaining/improving A4. Post hoc analyses showed 82% achieved a physiologic GC dose with crinecerfont regardless of A4 level; of these, 53% had normal A4. In contrast, 37% achieved a physiologic GC dose with placebo, and 49% had elevated A4 despite supraphysiologic GC dosing. Given the known adverse effects of elevated androgens and chronic supraphysiologic GC exposure, crinecerfont represents a therapeutic approach where the dual goals of reducing androgen excess and decreasing GC to a more physiologic range can be achieved. Presentation: Saturday, July 12, 2025
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".