Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension

Maria Fleseriu*, John Newell-Price*, Rosario Pivonello, Akira Shimatsu, Richard J. Auchus, Carla Scaroni, Zhanna Belaya, Richard A. Feelders, Greisa Vila, Ghislaine Houde, Rama Walia, Miguel Izquierdo, Michael Roughton, Alberto M. Pedroncelli, Beverly M.K. Biller

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Objective: To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing's disease (CD). Design/methods: A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) > 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study. Patients benefiting from osilodrostat at week 48 could enter the optional extension (ending when all patients had received ≥ 72 weeks of treatment or discontinued). Efficacy and safety were assessed for all enrolled patients from the core study baseline. Results: Median osilodrostat exposure from the core study baseline to study end was 130 weeks (range 1-245) and median average dose was 7.4 mg/day (range 0.8-46.6). The reduction in mean mUFC achieved during the core was maintained during the extension and remained ≤ ULN. Of 106 patients, 86 (81%) patients who entered the extension had mUFC ≤ ULN at week 72. Improvements in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism (fat pads, central obesity, rubor, striae, and hirsutism in females), and quality of life in the core study were also maintained or improved further during the extension. No new safety signals were reported; 15/137 (10.9%) and 12/106 (11.3%) patients discontinued for adverse events during the core and extension, respectively. Mean testosterone in females decreased towards baseline levels during the extension. Conclusions: Data from this large, multicentre trial show that long-term treatment with osilodrostat sustains cortisol normalisation alongside clinical benefits in most patients with CD and is well tolerated.

Original languageEnglish
Pages (from-to)531-541
Number of pages11
JournalEuropean Journal of Endocrinology
Volume187
Issue number4
Early online date16 Sep 2022
DOIs
Publication statusPublished - Oct 2022

Bibliographical note

Funding
This study was funded by Novartis Pharma AG; however, as of 12 July 2019, osilodrostat is an asset of Recordati. Financial support for medical editorial
assistance was provided by Recordati.

Copyright: © The authors 2022

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