ECE2023 Poster Presentations Pituitary and Neuroendocrinology (123 abstracts)
In the Phase III studies LINC 3 and LINC 4, osilodrostat was effective and well tolerated in patients of Asian and non-Asian origin with Cushing’s disease
Shimatsu Akira 1 , Beverly M.K. Biller 2 , Maria Fleseriu 3 , Rosario Pivonello 4 , Eun Jig Lee 5 , Leelawattana Rattana 6 , Jung Hee Kim 7 , Rama Walia 8 , Yerong Yu 9 , Zhihong Liao 10 , Andrea Piacentini 11 , Alberto Pedroncelli 12 & Peter Snyder 13
1Omi Medical Center, Kusatsu, Japan; 2Massachusetts General Hospital, Neuroendocrine and Pituitary Tumor Clinical Center, Boston, United States; 3Oregon Health & Science University, Pituitary Center, Departments of Medicine and Neurological Surgery, Portland, United States; 4Università Federico II di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy; 5Yonsei University, Department of Internal Medicine, Seoul, South Korea; 6Prince of Songkla University, Songkhla, Thailand; 7Seoul National University College of Medicine, Department of Internal Medicine, Seoul, South Korea; 8Postgraduate Institute of Medical Education and Research (PGIMER), Department of Endocrinology, Chandigarh, India; 9West China Hospital, Sichuan University, Chengdu, China; 10Sun Yat-sen University, Guangzhou, China; 11Recordati SpA, Milan, Italy; 12Recordati AG, Basel, Switzerland; 13Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Introduction: Osilodrostat (oral 11β-hydroxylase inhibitor) demonstrated rapid, sustained cortisol normalisation in Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734) in patients with Cushing’s disease (CD). Relative osilodrostat bioavailability is ~20% higher in Asian patients than other ethnicities; body weight is not a major determinant of this difference. This analysis of LINC 3 and LINC 4 evaluated osilodrostat efficacy and safety in Asian and non-Asian patients with CD.
Methods: Data were pooled from LINC 3 and LINC 4. LINC 3 comprised a 48-week (W) core phase, including an 8W randomised withdrawal for eligible patients. LINC 4 included an upfront 12W, double-blind, placebo-controlled period followed by 36W of open-label osilodrostat. Both studies had an optional extension. Outcomes were evaluated separately in Asian and non-Asian patients. Periods where patients received placebo were excluded.
Results: In total, 56/210 (27%) patients were of Asian origin, enrolled in China (n=16), South Korea (n=14), Japan (n=9), Thailand (n=9), India (n=7) and USA (n=1). Most non-Asian patients were Caucasian (n=138/154, 90%). Median (min−max) osilodrostat dose was 3.8 (1−25) and 7.3 mg/day (1−47) in Asian and non-Asian patients, respectively. Mean urinary free cortisol (mUFC) control was achieved at W48 and W72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients, respectively. Improvements from baseline in most cardiovascular and metabolic-related parameters and physical manifestations of hypercortisolism were similar across groups during treatment. Osilodrostat was generally well tolerated. The most common investigator-reported adverse events (AEs) were: adrenal insufficiency (44.6%), nausea (33.9%) and decreased appetite (26.8%) in Asian patients; nausea (45.5%), fatigue (40.9%) and headache (39.0%) in non-Asian patients. The most common serious AE in Asian and non-Asian patients was adrenal insufficiency (5.4% and 5.2%, respectively). Hypocortisolism-related AEs occurred in 58.9% of Asian and 40.3% of non-Asian patients, commonly reported by study investigators as adrenal insufficiency (44.6% and 22.1%). AEs related to pituitary tumour enlargement occurred in 21.4% of Asian and 9.1% of non-Asian patients. Arrhythmogenic potential and QT prolongation AEs were infrequent in all patients.
Conclusions: Osilodrostat demonstrated similar beneficial effects in Asian and non-Asian patients in mUFC control and improvements in cardiovascular and metabolic-related parameters and physical manifestations of hypercortisolism. The mean dose to achieve beneficial effects was lower in Asian than non-Asian patients. Osilodrostat was generally well tolerated in Asian and non-Asian patients; AEs related to hypocortisolism and pituitary enlargement were more frequent in Asian than non-Asian patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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