atumelnant (CRN04894) / Crinetics - LARVOL DELTA

Rapid And Sustained Reduction Of 11-oxygenated Androgens In Adults With Classic Congenital Adrenal Hyperplasia Following Once-daily Oral Atumelnant (CRN04894): Results From A 12-week, Phase 2, Open-label Study (ENDO 2025) - "Adults age ≥18-75 years with classic CAH taking stable doses of glucocorticoid (GC) replacement therapy (≥15 mg daily dose hydrocortisone equivalent) for ≥6 months and morning serum A4 level ≥1.5 times the upper limit of normal were enrolled in 3 dose cohorts of oral atumelnant, 40 mg, 80 mg, 120 mg once daily for 12 weeks. In conclusion, atumelnant results in rapid and substantial reductions of 11‑oxygenated androgens and the traditional biomarkers A4 and 17-OHP in patients with classic CAH. The reduction in total androgen burden may explain previously reported improvements in clinical outcomes within the 12-week time frame of this study."

Clinical • Late-breaking abstract • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Once-Daily Oral Atumelnant (CRN04894) Induces Rapid, Substantial, and Sustained Reductions of Androstenedione and 17‑Hydroxyprogesterone in Adults With Classical Congenital Adrenal Hyperplasia: Interim Results From a 12-Week, Phase 2, Open-Label Study (ENDO 2025) - P2 | "Adults with classic CAH (21-hydroxylase deficiency) on a stable dose of glucocorticoid (GC) replacement (≥15 mg hydrocortisone equivalent) for ≥6 months and androstenedione (A4) level ≥1.5 times the upper limit of normal (ULN) were enrolled in 3 dose cohorts (40 mg, 80 mg, or 120 mg) and received oral atumelnant once daily for 12 weeks. The most common treatment-emergent AEs were headache (n=7) and fatigue (n=5). Overall, rapid, substantial, and sustained reductions in A4 and 17-OHP were demonstrated with administration of atumelnant in adult patients with classical CAH."

Clinical • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Fatigue • Nephrology • Pain • Renal Disease

Reductions in Adrenal Volume in Patients With Congenital Adrenal Hyperplasia Receiving Once-Daily Oral Atumelnant (CRN04894): Interim Results From a 12-Week, Phase 2, Open-Label Study (ENDO 2025) - P2 | "In conclusion, through potent blockade of the adrenal MC2R and reduction or normalization of adrenal androgens, consistent reduction in adrenal size was demonstrated with 12 weeks of once-daily atumelnant. Furthermore, these results demonstrate the plasticity of hyperplastic adrenal tissue in adults with long-standing CAH and that ongoing adrenal hyperplasia is dependent on continued exposure to excess ACTH."

Clinical • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn) (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | N=30 ➔ 42 | Trial completion date: Mar 2025 ➔ Sep 2025 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders

CRN04894-09: An Extension Study to Evaluate Safety and Efficacy in Participants Treated With CRN04894 (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Initiation date: Nov 2024 ➔ Feb 2025

Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinetics Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Key Upcoming Milestones: Crinetics expects to begin enrollment of patients in two pivotal studies of atumelnant in CAH: Phase 3 in adults and Phase 2b/3 in pediatrics; Crinetics is also planning a study of atumelnant in Cushing’s disease. Enrollment of patients is expected to begin in late 2025 or early 2026."

New P2/3 trial • New P3 trial • New trial • Congenital Adrenal Hyperplasia • Cushing’s Disease

Advances in pharmacological treatment of Cushing's disease. (PubMed, Zhong Nan Da Xue Xue Bao Yi Xue Ban) - "Currently, three categories of medications are commonly used: 1) Drugs targeting somatostatin and/or dopamine receptors to inhibit pituitary adrenocorticotropic hormone (ACTH) synthesis (e.g., pasireotide, cabergoline); 2) drugs targeting adrenal cortex-related receptors to suppress steroid synthesis (e.g., ketoconazole, metyrapone, mitotane, and osilodrostat); 3) drugs acting on glucocorticoid receptors (e.g., mifepristone). Research on pharmacological treatments for Cushing's disease is ongoing, with new drugs such as seliciclib, CRN04894, fimepinostat, vorinostat, and SPI-62 currently in phase II clinical trial. The development of novel drugs holds promise for more precise and effective treatment for Cushing's disease patients."

Journal • Review • Cardiovascular • Cushing’s Disease • Endocrine Disorders

An Extension Study to Evaluate Safety and Efficacy in Participants Treated With CRN04894 (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P2 trial • Congenital Adrenal Hyperplasia • Endocrine Disorders

Atumelnant (crn04894) Induces Rapid And Sustained Reductions In Serum And Urine Cortisol In Patients With Acth-dependent Cushing Syndrome During A Phase 1b/2a, Single Center, 10-day, Inpatient, Open-label Study (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P1/2 data • Cushing’s Disease • Endocrine Disorders

Once Daily Oral Atumelnant (CRN04894) Induces Rapid And Profound Reductions Of Androstenedione And 17-hydroxyprogesterone In Participants With Classical Congenital Adrenal Hyperplasia: Initial Results From A 12-week, Phase 2, Open-label Study (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Discovery of CRN04894: A Novel Potent Selective MC2R Antagonist. (PubMed, ACS Med Chem Lett) - "Oral administration of 17h suppressed ACTH-stimulated corticosterone secretion in a dose-dependent manner at doses ≥3 mg/kg. With its satisfactory pharmaceutical properties, 17h was advanced to Phase 1 human clinical trials in healthy volunteers with the goal of moving into patient trials to evaluate CRN04894 for the treatment of ACTH-dependent diseases, including congenital adrenal hyperplasia (CAH) and Cushing's disease (CD)."

Journal • Congenital Adrenal Hyperplasia • Cushing’s Disease • Endocrine Disorders • MC4R

A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Phase classification: P1b/2a ➔ P1/2

Phase classification • Cushing’s Disease • Endocrine Disorders

Crinetics Pharmaceuticals Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initial data from Phase 2 study of paltusotine in carcinoid syndrome expected December 2023. The Phase 2 open-label study of paltusotine in carcinoid syndrome associated with neuroendocrine tumors is completing enrollment....Based on successful Phase 1 studies demonstrating pharmacologic proof-of-concept, Crinetics is advancing clinical studies of CRN04894 in both Cushing’s disease and congenital adrenal hyperplasia. Data from the ongoing studies are expected in the second half of 2024."

Clinical data • P2 data • Carcinoid Syndrome • Congenital Adrenal Hyperplasia • Cushing’s Disease