Endocrine Abstracts

Introduction: Potent 11β-hydroxylase inhibitor osilodrostat provides cortisol level control in patients with Cushing’s syndrome (CS), as demonstrated by the LINC clinical development programme in Cushing’s disease (CD) patients.1 We report data from year 1 of the prospective observational LINC6 study (NCT05382156), evaluating long-term safety and efficacy of osilodrostat in CS patients during 3 years of routine clinical practice.<p class="abstext"...

Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States. The MPOWERED trial (NCT02685709) showed that OOC were noninferior to injectable somatostatin receptor ligands (iSRLs; octreotide or lanreotide) in maintenance of biochemical control in patients previously responding to both treatments, as well as demonstrated improvements in patient-reported outcomes among patients receiving OOC.Objective:...

Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States who have previously responded to injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide). In previous phase 3 studies, the safety of OOC was shown to be consistent with iSRLs, without dose-dependent adverse reactions. In the double-blind, placebo-controlled period (DPC) of the CHIASMA OPTIMAL trial (NCT03252353), patients were randomized to twi...

Introduction: Osilodrostat (oral 11β-hydroxylase inhibitor) demonstrated rapid, sustained cortisol normalisation in Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734) in patients with Cushing’s disease (CD). Relative osilodrostat bioavailability is ~20% higher in Asian patients than other ethnicities; body weight is not a major determinant of this difference. This analysis of LINC 3 and LINC 4 evaluated osilodrostat efficacy and safety in Asian and non-Asia...

Introduction: Osilodrosat is a potent oral 11β-hydroxylase inhibitor. During the 24-week, single-arm, open-label period of the Phase III LINC 3 study (NCT02180217), osilodrostat treatment demonstrated rapid, sustained reduction in mean urinary free cortisol (mUFC) in most Cushing disease (CD) patients. In the subsequent 8-week, double-blind, randomized-withdrawal phase, a significantly higher proportion of patients receiving osilodrostat maintained normal mUFC at week (W)...

Introduction: During the 22-week LINC-2 study, the potent oral 11β-hydroxylase inhibitor osilodrostat normalized UFC in 15/19 (78.9%) patients with Cushing’s disease. Most common AEs were nausea, diarrhoea, asthenia, and adrenal insufficiency. This report describes 19-month results following an extension.Methods: Patients who were receiving clinical benefit at week 22 could enter the extension. Efficacy/safety is reported for patients who enter...

Introduction: The PAOLA study in patients with inadequately-controlled acromegaly (n=198) demonstrated superior efficacy of pasireotide long-acting release (LAR; 40 mg/60 mg) in biochemical control (GH <2.5 μg/l and normalized IGF-1) vs continued treatment with octreotide LAR 30 mg/lanreotide Autogel 120 mg (15.4% and 20.0% vs 0%). Here we report preliminary data from the extension phase of PAOLA at wk28.Methods: Pasireotide-LAR (40 mg/...

Background: Some patients with acromegaly do not achieve biochemical control despite receiving maximum-approved doses of currently available somatostatin analogues. This 24-week, randomized study assessed the multireceptor-targeted somatostatin analogue pasireotide LAR vs octreotide LAR/lanreotide Autogel in patients with inadequately controlled acromegaly.Methods: Eligible patients: ≥18 years with mean GH levels ≥2.5 μg/l and IGF1 level...

Introduction: In a Phase II study, osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD. We report the efficacy and safety of osilodrostat in a large CD patient population (NCT02180217).Methods: In this study, open-label osilodrostat was initiated at 2 mg bid in 137 adults with CD and mUFC > 1.5 × ULN, with dose adjustments every 2 weeks (range 1–30 mg bid) up to ...

Background: Patients with acromegaly responding to injectable somatostatin receptor ligands (SRL) are often treated for decades without deterioration of biochemical response (except for routine fluctuations in IGF-I control), unless there are changing clinical circumstances such as persistent or recurrent tumor growth. Oral octreotide capsules (OOC) have been formulated as a potential therapy for acromegaly and the safety and efficacy was evaluated in the CHIASMA OPTIMAL pivot...