Osilodrostat prior and new use in patients with endogenous cushing

Nicolas Scheyer; Frederic Castinetti; Eliza Geer; Stephanie Espiard; Celine Mouly; Laura Dichtel; Maria Fleseriu; Antoine Tabarin; Martin Reincke; Rosario Pivonello; Richard Feelders; Mouhaer Jeannie Le; Peppi Raunioniemi; Arnd Mueller; Irina Bancos

doi:10.1530/endoabs.110.P870

P870

Prev Next

Section Contents Cite

Endocrine Abstracts (2025) 110 P870 | DOI: 10.1530/endoabs.110.P870

ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)

Osilodrostat prior and new use in patients with endogenous cushing’s syndrome: 2-year interim analysis results (safety and effectiveness) from the real-world non-interventional LINC 6 study

Nicolas Scheyer ¹ , Frédéric Castinetti ² , Eliza Geer ³ , Stephanie Espiard ⁴ , Celine Mouly ⁵ , Laura Dichtel ⁶ , Maria Fleseriu ⁷ , Antoine Tabarin ⁸ , Martin Reincke ⁹ , Rosario Pivonello ¹⁰ , Richard Feelders ¹¹ , Jeannie Le Mouhaër ¹² , Peppi Raunioniemi ¹³ , Arnd Mueller ¹³ & Irina Bancos ¹⁴

Author affiliations

¹Département d’Endocrinologie, Diabétologie, et Nutrition, CHRU de Nancy, Hôpital Brabois et Université de Lorraine, Vandœuvre-lès-Nancy, France; ²Aix-Marseille University, INSERM, MMG, Department of Endocrinology, La Conception Hospital, Assistance Publique Hôpitaux de Marseille, Marseille, France; ³Multidisciplinary Pituitary and Skull Base Tumor Center, Departments of Medicine and Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States; ⁴CHU de Lille, Lille, France; ⁵Hôpital Larrey, CHU de Toulouse, Toulouse, France; ⁶Neuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA, United States; ⁷Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, United States; ⁸CHU de Bordeaux and Centre de Référence des Maladies Rares de la Surrénale, Bordeaux, France; ⁹Ludwig-Maximilians-Universität München, Munich, Germany; ¹⁰Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy; ¹¹Department of Internal Medicine, Endocrine Section, Erasmus Medical Center, Rotterdam, Netherlands; ¹²Recordati Rare Diseases SpA, Paris, France; ¹³Recordati AG, Basel, Switzerland; ¹⁴Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, United States

JOINT1096

Introduction: The ongoing prospective, non-interventional LINC 6 (NCT05382156) study evaluates long-term safety and effectiveness of osilodrostat, a potent 11β-hydroxylase inhibitor, in routine clinical practice over 3 years in patients with Cushing’s syndrome (CS). We report results from a prespecified 2-year interim analysis.

Methods: Adults with endogenous CS were enrolled in five countries (Europe/USA) where osilodrostat is approved and available. The primary objective is long-term safety and tolerability, evaluated by the rate of osilodrostat-related adverse events (AEs) and serious AEs (SAEs). Secondary effectiveness endpoints include change in mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC). Outcomes were analysed in patients who were prior (any time before study entry) or new users of osilodrostat. AE/SAE data are reported up to data cut-off (July 2024) in the safety population (≥1 dose, n = 206). Cortisol changes are reported in patients with assessments at baseline and month (M)6. All assessments are descriptive.

Results: Data were available for 205 patients: Cushing’s disease, n = 161; adrenal adenoma, n = 12; adrenal carcinoma, n = 2; bilateral adrenal nodular disease, n = 10; ectopic adrenocorticotropic hormone secretion, n = 17; other, n = 3. Among prior (n = 135) and new (n = 70) users, 74.1% and 78.6% were female, and mean (SD) age was 54.1 (13.9) and 50.8 (15.1) years, respectively. Median (min–max) on-study osilodrostat exposure and dose were 10.4M (0.0–20.8) and 5.0 mg/day (0.5–80.0) in prior users and 4.2M (0.4–19.6) and 4.7 mg/day (1.6–69.3) in new users. Thirty-one prior and 12 new users reported 75 and 30 AEs considered treatment related, most commonly (>6.0% of events) adrenal insufficiency (13.3%, n = 10/75), dizziness (8.0%, n = 6/75), diarrhoea and fatigue (both 6.7%, n = 5/75) among prior users and adrenal insufficiency (16.7%, n = 5/30), gastrointestinal disorder, hypokalaemia, headache, and abnormal hair growth (all 6.7%, n = 2/30 each) among new users. Seven (six [4.4%] prior, one [1.4%] new user) patients discontinued because of 11 (10 in prior, one in new user) treatment-related AEs. SAEs occurred in 9.6% (n = 13/135) of prior and 20.0% (n = 14/70) of new users; 7/21 (33.3%) and 4/24 (16.7%) SAEs were considered treatment related, respectively. At M6, mUFC and LNSC were normal in 67.6% (n = 25/37) and 35.3% (n = 6/17) of prior, and in 44.4% (n = 4/9) and 16.7% (n = 1/6) of new, users, respectively.

Conclusions: LINC 6 2-year interim data show the clinical utility of osilodrostat in a real-world setting for the management of CS in both prior and new users with differing aetiologies. AEs were as expected; few led to treatment discontinuation.