SAT-071 Long-Term Effect of Subcutaneous Pasireotide on Clinical and Quality of Life Endpoints in Patients with Cushing's Disease: Results from a Non-interventional Study

Abstract J. Bertherat: Consulting Fee; Self; Atterocor, Shire, HRA Pharma Rare Diseases, Novartis Pharmaceuticals, Corcept Therapeutics, Recordati Rare Diseases. Grant Recipient; Self; Novartis Pharmaceuticals, Pfizer, Inc., HRA Pharmaceuticals. S. Cannavò: None. C. Giordano: None. M. Detomas: None. C. Scaroni: None. G. Raverot: Consulting Fee; Self; Novartis Pharmaceuticals, Pfizer, Inc., Ipsen, Recordati Rare Diseases, Crinetics, Novo Nordisk, Amolyt Pharma. Grant Recipient; Self; Novartis Pharmaceuticals, Pfizer, Inc., Ipsen, Recordati Rare Diseases, Crinetics, Novo Nordisk, Amolyt Pharma. Research Investigator; Self; Novartis Pharmaceuticals, Pfizer, Inc., Ipsen, Recordati Rare Diseases, Crinetics, Novo Nordisk, Amolyt Pharma. Speaker; Self; Novartis Pharmaceuticals, Pfizer, Inc., Ipsen, Recordati Rare Diseases, Crinetics, Novo Nordisk, Amolyt Pharma. J. Schopohl: Grant Recipient; Self; Crinetics, Recordati, Camurus. C. Georgescu: Speaker; Self; Recordati, Pfizer, Inc., Novo Nordisk. A. Piacentini: Employee; Self; Recordati. A. Mueller: Employee; Self; Recordati. J. Stermenska: Employee; Self; Recordati. F. Bogazzi: None. Introduction: Cushing’s disease (CD) causes chronic hypercortisolism associated with impaired quality of life (QoL), long-term morbidity and increased mortality risk. The efficacy and safety of subcutaneous (sc) pasireotide, a second-generation somatostatin receptor ligand, were demonstrated in CD patients (pts) in a Phase III study (NCT00434148). In the USA and Europe, pasireotide sc is indicated for adults with CD for whom surgery is not an option or has not been curative. We report data from a non-interventional study (NCT02310269) evaluating the long-term safety and efficacy of pasireotide sc for CD pts. Methods: Adults with CD who were treated with pasireotide sc were monitored for 3 years. Pts were grouped by time of pasireotide sc initiation: at study entry in ‘new use’ (NU) pts and prior to study entry in ‘prior use’ (PU) pts. The primary endpoint was incidence of pasireotide sc related adverse events (AEs) and serious AEs. Secondary endpoints reported herein include changes from baseline (B) in CD signs and symptoms and pt-reported QoL outcomes. Results: 152 pts (45 NU, 107 PU) formed the full analysis set. Median (min-max) pasireotide sc exposure in the safety set (n=148 [43 NU, 105 PU]) was: NU, 7 (0-37) months (Ms) on study; PU, 34 (0-132) Ms from drug initiation. 50/105 (48%) PU pts received pasireotide sc for >36 Ms. Median (min-max) daily dose on study (n=148) was 1200 (300-1800) μg/day. 123/152 (81%) pts discontinued study treatment (NU, n=41/45 [91%]; PU, n=82/107 [77%]). The proportion of full responders (mean urinary free cortisol ≤ upper limit of normal [138 nmol/24h]) at B, M12, M24, M36 were (% [n]): NU, 17 (4/23), 30 (3/10), 71 (5/7), 33 (1/3); PU, 67 (30/45), 76 (31/41), 67 (24/36), 60 (9/15). Median (min-max) systolic blood pressure (SBP) decreased in NU pts (B, 130 [97-180] mmHg; M36, 110 [106-150] mmHg) and remained stable in PU pts (B, 130 [90-234] mmHg; M36, 128 [108-150] mmHg). Median (min-max) body weight decreased in both groups from B (NU, 84 [49-141] kg; PU, 79 [41-152] kg) to M36 (NU, 67 [55-77] kg; PU, 71 [40-131] kg). Median (min-max) body mass index (BMI) also decreased from B (NU, 30 [21-49]; PU, 29 [19-68]) to M36 (NU, 25 [24-27]; PU, 27 [20-49]). In both groups, there was a general trend over time to improved CD symptoms, including facial rubor, bruising and fat pads. Median (min-max) CushingQoL score at B was: NU, 52 (8-65; n=16); PU, 42 (8-75; n=25), and at M36: NU, 67 (67-67; n=1); PU, 50 (35-92; n=5). Conclusions: The proportion of full responders increased over time in NU pts and remained stable in PU pts. Generally, measures of CD signs (SBP, body weight, BMI) improved at M36 in both groups, with greater numerical improvements in NU than PU pts. Data should be interpreted with caution as few pts were followed up to M36; however, trends were present at M12 in more pts and indicate that pasireotide sc is an effective long-term therapy for adults with CD for whom surgery has failed or is not an option. Saturday, June 1, 2024