Endocrine Abstracts

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...

Background: ACROSTUDY is an open-label, non-interventional post-authorization safety study that began in 2004 to evaluate safety in at least 1000 acromegaly patients treated with the GH receptor antagonist pegvisomant (PEGV). This commitment was fulfilled in Jan 2013. ACROSTUDY was later amended to enroll an additional 110 patients that were naïve/semi-naive to PEGV treatment. Semi-naïve patients are defined as not having received PEGV therapy for at least 6 months p...

Background: Cushing’s syndrome (CS) has numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole is a ketoconazole stereoisomer in clinical trials for treatment of CS.Methods: SONICS is a prospective, open-label, phase 3 maintenance-of-benefit study in adults with confirmed CS and mean urinary free cortisol (mUFC) of ≥1.5x upper limit of normal (ULN). Repeated hospitalization due to hyperglycemia or any complication related t...

Background: Pasireotide is a multireceptor-targeted somatostatin analogue that predominantly binds to somatostatin receptor subtype 5 (SSTR5) and provides sustained control of urinary free cortisol (UFC) levels in some patients with Cushing’s disease (CD). Cabergoline is a dopamine D2 receptor agonist with efficacy in some patients with CD. Most corticotropinomas co-express SSTR5 and D2, providing rationale for combination treatment with pasireotide and cabergoline. Resul...

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...

Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.Methods: There were two study groups. Previous LINC 1 participants (follow-up coh...

Background: Many patients with acromegaly report limitations of long-acting somatostatin receptor ligand (SRL) injections, including ongoing disease symptoms near cycle-end and injection-site pain. Oral octreotide capsules (OOC) may provide an alternative to monthly injections. The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of OOC in patients with acromegaly controlled on injectable SRLs.Methods: A multinational, randomized, placebo-contr...

Background: Injectable somatostatin receptor ligands (SRLs) are currently the most widely used therapy for acromegaly. Oral octreotide capsules (OOC) are a potential therapy for acromegaly; the safety and efficacy were evaluated in the CHIASMA OPTIMAL pivotal study (Samson et al. ENDO 2020). As reported, mean IGF-I levels of the OOC group were maintained within normal range at end of treatment in all patients. However, some patients may not respond to OOC treatment (2...

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...

IntroductionOsilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD during the 48-week (W) core phase of a Phase III study (LINC3: NCT02180217). We present efficacy and safety results following an extension to LINC3.MethodsCD patients with mUFC > 1.5× upper limit of normal (ULN) received osilodrostat during the core. Patients b...