Long-term efficacy and safety of osilodrostat in patients with Cushing’s disease: results from the LINC 4 study extension

Mônica Gadelha*, Peter J. Snyder, Przemysław Witek, Marie Bex, Zhanna Belaya, Adina F. Turcu, Richard A. Feelders, Anthony P. Heaney, Michaela Paul, Alberto M. Pedroncelli, Richard J. Auchus

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Abstract

Objective: 

To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing’s disease. 

Methods: 

The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushing’s disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed. 

Results: 

Of 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushing’s disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports. 

Conclusion: 

Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushing’s disease. 

Clinical trial registration: 

ClinicalTrials.gov,

Original languageEnglish
Article number1236465
Number of pages14
JournalFrontiers in Endocrinology
Volume14
DOIs
Publication statusPublished - 23 Aug 2023

Bibliographical note

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

Publisher Copyright:
Copyright © 2023 Gadelha, Snyder, Witek, Bex, Belaya, Turcu, Feelders, Heaney, Paul, Pedroncelli and Auchus.

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