Long-term post-trial extension of osilodrostat therapy in selected Canadian patients with Cushing disease from the LINC 3 and LINC 4 programs
4 affiliations
- 1Division of Endocrinology, Department of Medicine, Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- 2Division of Endocrinology, Department of Medicine, University of Sherbrooke, Sherbrooke, QC, Canada
- 3Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, Edmonton, AB, Canada
- 4Division of Endocrinology and Metabolism, Dalhousie University, Halifax, NS, Canada
Abstract
Background: Long-term outcomes of selected patients who continue osilodrostat for Cushing disease after clinical-trial participation remain incompletely described.
Methods: We retrospectively analyzed a selected multicenter post-trial cohort of Canadian patients with Cushing disease previously enrolled in LINC 3 (NCT02180217) or LINC 4 (NCT02697734) who continued osilodrostat in the global roll-over study and, when applicable, in a Canadian investigator-initiated extension phase (ISS-CA-2023; NCT06131580). The dataset included 11 Canadian osilodrostat-exposed LINC participants who entered post-trial roll-over follow-up; 7 subsequently entered the Canadian investigator-initiated extension, whereas 4 discontinued during earlier follow-up for defined reasons. For longitudinal efficacy analyses, baseline and time zero were defined as first osilodrostat exposure in the parent LINC study; week 14 refers to week 14 after osilodrostat initiation. The main outcomes were time to first mean urinary free cortisol (mUFC) control, durability of control, long-term dose evolution, pituitary tumor surveillance, and safety.
Results: Eleven selected Canadian patients received continued osilodrostat, and all achieved first biochemical control after a median of 5 weeks (range: 2–12). Median mUFC decreased from 2.65 × ULN at parent-study baseline to 0.56 × ULN at week 14; these descriptive values were not used for inferential testing. Seven patients remained on therapy long term; at the last follow-up, six of seven had controlled mUFC after a median exposure of 98 months (range: 83 to 121). Maintenance doses varied widely, with a median last-visit dose of 6 mg/day (range: 0.125 to 40), and several patients required progressive down-titration over time. Hypocortisolism/adrenal-insufficiency events were common and generally managed with dose interruption or reduction and temporary glucocorticoid replacement. Clinically significant pituitary tumor enlargement leading to discontinuation and surgery occurred in two patients.
Conclusion: In this selected Canadian post-trial continuation cohort, osilodrostat was associated with rapid initial biochemical control and durable long-term control in many patients for up to 10 years. The findings support the feasibility of long-term individualized osilodrostat management in selected patients continuing therapy after LINC 3/LINC 4 participation, with ongoing need for dose adaptation and surveillance for adrenal insufficiency and pituitary tumor behavior.
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BibTeX
@article{martelduguech2026longterm,
title = {{Long-term post-trial extension of osilodrostat therapy in selected Canadian patients with Cushing disease from the LINC 3 and LINC 4 programs}},
author = {Luciana Martel-Duguech and Ghislaine Houde and Constance Chik and Syed Ali Imran and André Lacroix},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1902818},
url = {https://doi.org/10.3389/fendo.2026.1902818},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-term post-trial extension of osilodrostat therapy in selected Canadian patients with Cushing disease from the LINC 3 and LINC 4 programs
AU - Luciana Martel-Duguech
AU - Ghislaine Houde
AU - Constance Chik
AU - Syed Ali Imran
AU - André Lacroix
PY - 2026
DA - 2026/10/12
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1902818
UR - https://doi.org/10.3389/fendo.2026.1902818
AB - Background: Long-term outcomes of selected patients who continue osilodrostat for Cushing disease after clinical-trial participation remain incompletely described. Methods: We retrospectively analyzed a selected multicenter post-trial cohort of Canadian patients with Cushing disease previously enrolled in LINC 3 (NCT02180217) or LINC 4 (NCT02697734) who continued osilodrostat in the global roll-over study and, when applicable, in a Canadian investigator-initiated extension phase (ISS-CA-2023; NCT06131580). The dataset included 11 Canadian osilodrostat-exposed LINC participants who entered post-trial roll-over follow-up; 7 subsequently entered the Canadian investigator-initiated extension, whereas 4 discontinued during earlier follow-up for defined reasons. For longitudinal efficacy analyses, baseline and time zero were defined as first osilodrostat exposure in the parent LINC study; week 14 refers to week 14 after osilodrostat initiation. The main outcomes were time to first mean urinary free cortisol (mUFC) control, durability of control, long-term dose evolution, pituitary tumor surveillance, and safety. Results: Eleven selected Canadian patients received continued osilodrostat, and all achieved first biochemical control after a median of 5 weeks (range: 2–12). Median mUFC decreased from 2.65 × ULN at parent-study baseline to 0.56 × ULN at week 14; these descriptive values were not used for inferential testing. Seven patients remained on therapy long term; at the last follow-up, six of seven had controlled mUFC after a median exposure of 98 months (range: 83 to 121). Maintenance doses varied widely, with a median last-visit dose of 6 mg/day (range: 0.125 to 40), and several patients required progressive down-titration over time. Hypocortisolism/adrenal-insufficiency events were common and generally managed with dose interruption or reduction and temporary glucocorticoid replacement. Clinically significant pituitary tumor enlargement leading to discontinuation and surgery occurred in two patients. Conclusion: In this selected Canadian post-trial continuation cohort, osilodrostat was associated with rapid initial biochemical control and durable long-term control in many patients for up to 10 years. The findings support the feasibility of long-term individualized osilodrostat management in selected patients continuing therapy after LINC 3/LINC 4 participation, with ongoing need for dose adaptation and surveillance for adrenal insufficiency and pituitary tumor behavior.
SN - 1664-2392
ER -