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Endocrine Abstracts (2021) 73 PEP8.5 | DOI: 10.1530/endoabs.73.PEP8.5

ECE2021 Presented Eposters Presented ePosters 8: Pituitary and Neuroendocrinology (8 abstracts)

Osilodrostat provides sustained control of urinary free cortisol in patients with Cushing’s disease: final results from a prospective, open-label study (LINC 2)

Maria Fleseriu 1 , Beverly Biller 2 , Jerome Bertherat 3 , Jacques Young 4 , Giorgio Arnaldi 5 , Paul O’Connell 6 , Miguel Izquierdo 7 , Alberto Pedroncelli 8 & Rosario Pivonello 9

1Oregon Health & Science University, Pituitary Center, Departments of Medicine and Neurological Surgery, Portland, USA; 2Massachusetts General Hospital, Neuroendocrine and Pituitary Tumor Clinical Center, Boston, USA; 3Hôpital Cochin, AP-HP and Université de Paris, Department of Endocrinology, Centre de Référence des Maladies Rares de la Surrénale, Paris, France; 4Paris-Sud University and Paris Saclay University, Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Department of Endocrinology, Le Kremlin-Bicêtre, France; 5Polytechnic University of Marche, Division of Endocrinology, Department of Clinical and Molecular Sciences, Ancona, Italy; 6Novartis Ireland Limited, Dublin, Ireland; 7Novartis Pharma AG, Basel, Switzerland; 8Recordati AG, Basel, Switzerland; 9Università Federico II di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy


The oral 11β-hydroxylase inhibitor, osilodrostat, normalized mean urinary free cortisol (mUFC) in 79% (15/19) of patients with Cushing’s disease at the end of the 22-week core LINC 2 study. Long-term efficacy and safety data following an optional extension phase are reported here.


Patients with clinical benefit at week 22 could continue receiving osilodrostat during the extension; dose adjustments were permitted based on efficacy/safety. Response status was assessed over time: controlled mUFC (≤ULN) or partially controlled mUFC (>ULN but ≥50% decrease from baseline). Efficacy and safety were assessed for all patients from core baseline to study end.


Of 19 patients enrolled in the core study (female : male 14:5; mean [S.D.] age 36.8 years [8.4]), 16 entered the extension and 8 continued treatment until study end. Median (range) osilodrostat exposure was 282 weeks (2–351). mUFC decreased from 9.9xULN at baseline to ≤ULN by week 4, remaining stable thereafter. At each extension-phase assessment up to month 70, 50–88% of patients had controlled mUFC, and up to 18% were partially controlled. Mean (S.D.) percentage change in clinical signs from baseline to last assessment were: fasting plasma glucose, –10.8% (22.1) (baseline: 105.6 mg/dl [49.2]); HbA1c, –2.1% (9.0) (baseline: 5.7% [0.7]); systolic BP, –3.3% (12.6) (baseline: 132.6 mmHg [11.6]); diastolic BP, –2.0% (10.4) (baseline: 85.0 mmHg [6.5]); BMI, –5.9% (8.8) (baseline: 30.7 kg/m2 [7.0]). Nine patients discontinued treatment, mostly because of AEs or no longer requiring treatment (n = 3 each). The most common AEs during the overall treatment period were nausea (n = 10), adrenal insufficiency, and headache (n = 9 each). AEs related to hypocortisolism and adrenal hormone precursor accumulation occurred in 11 (mostly adrenal insufficiency, n = 9) and 12 patients (mostly hypertension, n = 4), respectively; most were grade 1/2 and managed with dose adjustment/interruption and/or additional therapy. Mean (S.D.) plasma ACTH increased from 1.8xULN (0.9) at baseline to 7.1xULN (12.3) at week 22 and 6.9xULN (12.6) at last assessment. Mean (S.D.) 11-deoxycortisol increased from 1.2xULN (1.3) at baseline to 13.6xULN (12.2) at week 22 and 3.6xULN (4.2) at last assessment. In females, mean (S.D.) testosterone increased from 0.8xULN (0.4) at baseline to 2.4xULN (2.1) at week 22 and 1.0xULN (0.9) at last assessment. AEs of hirsutism were reported in two female patients.


Osilodrostat provided rapid and sustained reductions in mUFC for up to 6 years of treatment, with improvements in clinical signs of hypercortisolism. Osilodrostat was well tolerated, with no new safety signals during long-term treatment.

Volume 73

European Congress of Endocrinology 2021

22 May 2021 - 26 May 2021

European Society of Endocrinology 

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