Endocrine Abstracts

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

Introduction: Osilodrostat decreases cortisol production by inhibiting 11β-hydroxylase, increasing adrenal hormones above the blockade. Here, we describe these effects of osilodrostat and associated adverse events (AEs). The efficacy and safety of osilodrostat in patients with Cushing’s disease (CD) were confirmed in the published Phase III, prospective LINC 3 study (NCT02180217).Methods: 137 patients with CD (mUFC >1.5x upper limit of norm...

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hyper...

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...

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: 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...