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
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».