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

Autor:	Gadelha M; Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Snyder PJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Witek P; Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw, Warsaw, Poland., Bex M; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium., Belaya Z; Department of Neuroendocrinology and Bone Disease, Endocrinology Research Centre, Moscow, Russia., Turcu AF; Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States., Feelders RA; Department of Internal Medicine, Endocrine Section, Erasmus Medical Center, Rotterdam, Netherlands., Heaney AP; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States., Paul M; Novartis Pharma AG, Basel, Switzerland., Pedroncelli AM; Recordati AG, Basel, Switzerland., Auchus RJ; Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States.; Department of Pharmacology, University of Michigan, Ann Arbor, MI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Aug 23; Vol. 14, pp. 1236465. Date of Electronic Publication: 2023 Aug 23 (Print Publication: 2023).
DOI:	10.3389/fendo.2023.1236465
Abstrakt:	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, identifier NCT02180217. Competing Interests: Author MG has received speaker fees from Recordati, Ipsen, Crinetics Pharmaceuticals, and Novo Nordisk and attended advisory boards for Novo Nordisk, Recordati, Ipsen, and Crinetics Pharmaceuticals. Author PS reports consultancy for Teva Pharmaceuticals. Author PW reports receiving travel grants and speaker fees from Novartis, Ipsen, Recordati, Novo Nordisk, Strongbridge Biopharma now Xeris Pharmaceuticals, and Lilly. Author MB reports receiving travel grants from Novartis, Ipsen, and Pfizer and consultancy for Novartis. Author ZB has nothing to disclose. Author AT reports consultancy for CinCor and PhaseBio. Author RF reports consultancy for HRA Pharma and Recordati and a research grant from Corcept Therapeutics. Author AH reports speaker fees from Chiasma and Ipsen and has been an advisor to Strongbridge Biopharma now Xeris Pharmaceuticals, Novo Nordisk, and Lundbeck Pharma. Author MP is employed by the company Novartis Pharma AG. Author AP was employed by the company Recordati AG at the time of manuscript development. Author RA reports grants and personal fees from Xeris Pharmaceuticals, Spruce Biosciences, Neurocrine Biosciences, Corcept Therapeutics, Diurnal Ltd, Sparrow Pharmaceuticals, and Novartis and personal fees from Adrenas Therapeutics, Janssen Pharmaceuticals, Quest Diagnostics, Crinetics Pharmaceuticals, PhaseBio Pharmaceuticals, H Lundbeck A/S, Novo Nordisk, and Recordati Rare Diseases. (Copyright © 2023 Gadelha, Snyder, Witek, Bex, Belaya, Turcu, Feelders, Heaney, Paul, Pedroncelli and Auchus.)
Databáze:	MEDLINE
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