ECE2021 Oral Communications Oral Communications 3: Pituitary and Neuroendocrinology (6 abstracts)
Osilodrostat is an effective and well-tolerated treatment for Cushing’s Disease (CD): Results from a Phase III, multicentre, randomized, double-blind study with an initial placebo-controlled phase (LINC 4)
Monica Gadelha 1 , Marie Bex 2 , Richard Feelders 3 , Anthony Heaney 4 , Richard Auchus 5 , Aleksandra Gilis-Januszewska 6 , Przemyslaw Witek 7 , Zhanna Belaya 8 , Zhihong Liao 9 , Chih Hao Chen Ku 10 , Davide Carvalho 11 , Michael Roughton 12 , Judi Wojna 13 , Georg Hofstetter 12 , Alberto Pedroncelli 14 & Peter Snyder 15
1Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2University Hospitals Leuven, Leuven, Belgium; 3Erasmus Medical Center, Rotterdam, Netherlands; 4David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; 5University of Michigan, Ann Arbor, Ann Arbor, United States; 6Jagiellonian University Medical College, Krakow, Poland; 7Medical University of Warsaw, Warsaw, Poland; 8Endocrinology Research Centre, Moscow, Russian Federation; 9The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 10Clinica Los Yoses, San Pedro, Costa Rica; 11Centro Hospitalar Universitário de São João, Porto, Portugal; 12Novartis Pharma AG, Basel, Switzerland; 13Novartis Pharmaceuticals Corporation, East Hanover, United States; 14Recordati AG, Basel, Switzerland; 15Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Introduction
Osilodrostat, a potent, oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD during a Phase III, randomized-withdrawal study. We now report findings from a Phase III study of osilodrostat in patients with CD that featured an initial double-blind, randomized, placebo-controlled period (LINC 4; NCT02697734).
Methods
Adults with CD (mUFC > 1.3 × ULN) were randomized 2:1 to osilodrostat 2 mg bid or matching placebo for a 12-week (W) double-blind period; dose adjustments (range 1–20 mg bid) were permitted based on efficacy at W2, W5, and W8 and tolerability. From W12 to W48, all patients received open-label osilodrostat, with dose adjustments permitted (range 1–30 mg bid). At W48, patients could enter an optional extension. Primary endpoint: proportion of randomized patients who received 31 treatment dose with mUFC ≤ ULN at W12.
Results
Seventy-three patients were randomized and received osilodrostat (n = 48) or placebo (n = 25; baseline median [range] mUFC 2.5 × ULN [0.7–12.5] vs 2.2 × ULN [0.2–18.9]). At W12, 77% of osilodrostat recipients achieved mUFC ≤ ULN vs 8% on placebo (OR 43.4; 95% CI 7.1–343.2; P < 0.0001). At W36, 81% (95% CI 69.9–89.1) of osilodrostat recipients achieved mUFC ≤ ULN (key secondary endpoint). Median time to first controlled mUFC response for osilodrostat patients was 35 days (95% CI 34–52). At data cut-off (25 February 2020), median osilodrostat exposure was 71.7 vs 62.3 weeks for patients initially randomized to osilodrostat vs placebo (median [IQR] osilodrostat dose: 4.7 [3.8–9.0] vs 6.0 mg/day [3.7–9.7]). Up to W12, three osilodrostat recipients discontinued, one because of an AE (arthralgia), vs 0 with placebo. Most commonly reported AEs by W12 were decreased appetite (38% osilodrostat vs 16% placebo), arthralgia (35% vs 8%) and nausea (31% vs 12%). AEs related to hypocortisolism (15% osilodrostat vs 0% placebo) and adrenal hormone precursor accumulation (44% vs 36%) were mostly grade 1/2 and resolved with dose reduction/interruption and/or concomitant medication. Most common AEs occurring on osilodrostat treatment during the overall study period were arthralgia (45%), decreased appetite (45%), fatigue (38%), nausea (37%) and headache (33%). Improvements in clinical signs of hypercortisolism, including systolic/diastolic blood pressure and HbA1c, were observed with osilodrostat at W12 and W48.
Conclusions
Osilodrostat was superior to placebo at normalizing mUFC at W12 (77% vs 8%). Improvements in mUFC were sustained at W36. Few patients discontinued treatment because of AEs; hypocortisolism-related AEs were infrequent and manageable. We conclude that osilodrostat is a highly effective and well-tolerated treatment for patients with CD.
Volume 73
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more