SUN-073 Long-Term Safety of Pasireotide in Patients With Cushing's Disease: Final Results From a 10-Year Open-Label Phase IV Rollover Study (B2412)

Abstract Disclosure: W. Gallardo: Ipsen, Merck, Novartis Pharmaceuticals, Pfizer, Inc., Recordati Rare Diseases. C. De Block: A Menarini Diagnostics, Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Indigo Diabetes. Z. Hussein: Abbott Laboratories, Boehringer Ingelheim, Novartis Pharmaceuticals, Novo Nordisk, Zuellig Pharma Therapeutics. E. Grineva: Ipsen, Pfizer, Inc., Recordati Rare Diseases, Merck. N. Kapoor: None. J.M. Escalante Pulido: None. G. Rollin: Abbott Laboratories, AstraZeneca, Bayer, Inc., Merck Serono, Novo Nordisk. R. Baggenstoss: None. A. Piacentini: Recordati. A. Mueller: Recordati Rare Diseases. M. Gadelha: Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, Recordati Rare Diseases. Introduction: The long-term safety of pasireotide (a second-generation, multireceptor-targeted somatostatin receptor ligand) in patients (pts) with Cushing’s disease (CD), acromegaly and other rare endocrine disorders was assessed in an open-label, multicenter, Phase IV rollover study (B2412; NCT01794793). Final data are reported for CD pts who received pasireotide for ≤10 years during the rollover. Methods: Pts who were judged by the investigator to be benefiting from pasireotide at parent study end were eligible to enter the rollover and initially remained on the same pasireotide dose. Data are reported for CD pts from 4 parent studies who received pasireotide long-acting release (LAR; n=33) or subcutaneous (sc; n=29) and ≥1 dose during the rollover (except for 1 pt who only received pasireotide sc in the parent study). The primary objective of the rollover was to evaluate long-term pasireotide safety, assessed by frequency of adverse events (AEs)/serious AEs (SAEs). Data are reported from start to end of the rollover, unless otherwise stated. Results: Overall, 62 CD pts from 15 countries entered the rollover to receive pasireotide LAR or sc; 66.1% (n=41) completed treatment and 33.9% (n=21) discontinued, most commonly because of unsatisfactory therapeutic effect (12.9%, n=8). Median (min-max) duration of exposure and average dose from parent study baseline to rollover end was 7.4 years (2.7-9.9) and 32.6 mg/month (6-49) for pasireotide LAR and 5.8 years (0.6-15.8) and 469.3 µg/day (0-1661) for pasireotide sc. AEs, regardless of study drug relationship (pasireotide LAR and sc), were reported in 77.4% (n=48) of pts, most commonly (≥10% of pts) nasopharyngitis (24.2%, n=15), pharyngitis, diarrhea (each 14.5%, n=9), hypoglycemia, urinary tract infection and back pain (each 12.9%, n=8). Hyperglycemia and diabetes mellitus (DM) were reported in 2 and 4 pts, respectively. 62.9% (n=39) of pts required additional therapy to manage AEs, most commonly for nasopharyngitis (16.1%, n=10). 1 and 4 pts required additional therapy to manage hyperglycemia and DM, respectively. 9.7% (n=6) of pts required dose interruption/adjustment to manage AEs, most commonly for endocrine disorders (Cushing’s syndrome and hyperadrenocorticism, each 1.6%, n=1). In total, 4 pts (6.5%) discontinued treatment because of AEs (COVID-19, hyperglycemia, increased glycated hemoglobin, muscular weakness; each n=1). SAEs were reported in 33.9% (n=21) of patients, most commonly cholelithiasis (4.8%, n=3). 4 patients died during the rollover (colon cancer, COVID-19, pneumonia, septic shock; each n=1). No new safety signals were identified. Conclusion: Pasireotide is a well-tolerated long-term treatment option for CD pts, with pts having received treatment for ≤16 years from parent study entry. Few pts discontinued because of AEs, including hyperglycemia, and hyperglycemia was infrequent during the study. Presentation: Sunday, July 13, 2025