Endocrine Abstracts

Background: Cushing’s disease (CD) is associated with hypercortisolism-induced cardiovascular morbidity and mortality and impaired patient quality of life (QoL). We report long-term effects of osilodrostat (potent 11β-hydroxylase inhibitor) on cardiovascular/metabolic-related risk factors, physical features of hypercortisolism and QoL in CD patients following the core and extension phases of the LINC 4 study (NCT02697734).Methods: LINC 4 compri...

Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from subjects with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, open-label extension study are reported here. Prior to Advance, subjects previously completed one of two Phase 2 parent studies, Evolve (NCT03792555, with normal IGF-1 using injected lo...

Introduction: Acromegaly is associated with significant morbidity and reduced quality of life. A robust clinical programme (14 trials) established pasireotide as an effective second-generation somatostatin receptor ligand for the treatment of various endocrine conditions, including acromegaly. Patients who completed a previous pasireotide trial and continued to receive clinical benefit, according to the parent study investigator, could continue treatment in the B2412 rollover ...

Introduction: In two Phase III studies (LINC3, NCT02180217; LINC4, NCT02697734), osilodrostat, (potent oral 11β-hydroxylase inhibitor), provided rapid, sustained reductions in mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC), alongside improvements in clinical signs of hypercortisolism and health-related quality of life (HRQoL), in Cushing’s disease (CD) patients. mUFC and LNSC are recommended for monitoring treatment response. We assessed wh...

Introduction: Phase II (LINC2, NCT01331239) and Phase III (LINC3, NCT02180217; LINC4, NCT02697734) studies showed that osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term treatment for Cushing’s disease patients. In this LINC programme pooled analysis, we examined how dose uptitration and adjustments during long-term maintenance can provide rapid, sustained mean urinary free cortisol (mUFC) control, and minimise AEs.<p class="abstext...

Introduction: A robust clinical programme of 14 trials demonstrated pasireotide as an effective treatment for patients with rare endocrine disorders, including acromegaly and Cushing’s disease (CD). Patients with acromegaly or CD have significant morbidity, reduced quality of life and, if inadequately treated, higher mortality risk than the general population. This 8-year interim analysis evaluated long-term safety of pasireotide treatment in patients with acromegaly, CD ...

Introduction: High affinity binding of pasireotide for both sst2 and sst5 leads to its enhanced efficacy in treatment of acromegaly but results in decreased secretion of insulin, incretins (GLP-1 and GIP) and, to a lesser extent, glucagon. Metformin may be a good option in patients with acromegaly experiencing hyperglycaemia with pasireotide as it improves GLP-1 secretion. We analysed data from a 12-month, Phase III, randomised study in medically naï...

Introduction: EDIs with LAN-ATG therapy may help improve the burden associated with long-term acromegaly management. The LEAD study evaluated the efficacy and safety of this approach by switching from OCT-LAR conventional dosing to LAN-ATG EDI.Methods: LEAD was a multinational, multicentre, open-label, non-comparative study. Acromegalic patients with normal IGF1 after OCT-LAR 10 or 20 mg injections every 4 weeks for ≧6 months were switched to LAN-...

Introduction: LNSC has shown high sensitivity and specificity for the initial diagnosis of CD and detection of disease recurrence; however, the use of LNSC to monitor medical treatment of CD is not well established. The results of an exploratory analysis evaluating changes in LNSC in CD patients receiving long-acting pasireotide during a Phase III study (CSOM230G2304; Lacroix et al. Lancet Diabetes Endocrinol 2018) are reported here.Methods: Pat...

Long-acting somatostatin receptor ligands (LA-SRLs) are a first line medical treatment for acromegaly but require monthly parenteral administration. Paltusotine (CRN00808) is a nonpeptide, small molecule somatostatin type 2 (SST2) receptor agonist with high oral bioavailability (70%), suitable for once daily, oral dosing. The recently reported results of the ACROBAT Edge study (NCT03789656) suggest that patients with acromegaly treated with injected SRLs can switch to once dai...