SAT-563 PASIPHY: Phase II Study to Evaluate the Efficacy and Safety of Pasireotide Treatment for Patients With Post-bariatric Hypoglycemia

Abstract Disclosure: T. McLaughlin: Recordati Rare Diseases. A. Ciudin: AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi. J. Tack: Recordati Rare Diseases. T. Tan: AstraZeneca, Recordati Rare Diseases, Dexcom, Zihipp Ltd. A.J. Torres: Recordati Rare Diseases. A. Piacentini: Recordati. W. Agbotounou: Recordati Rare Diseases. A. Mueller: Recordati Rare Diseases. M.E. Patti: Alpha Sight, Boxer Capital, Cello, MBX Biosciences, Premier, Spruce Biosciences, Dexcom, Fractyl Laboratories, Recordati Rare Diseases. Introduction: Post-bariatric hypoglycemia (PBH) complicates up to 38% and 12% of gastric bypass and vertical sleeve gastrectomy surgeries, respectively. PBH, caused by rapid gastric emptying and excessive glucagon-like peptide 1 (GLP-1) and insulin secretion, is characterized by frequent postprandial hyperinsulinemic hypoglycemic episodes and neuroglycopenic symptoms. Pharmacologic approaches to address this unmet clinical need could include somatostatin receptor ligands. Pasireotide binds with high affinity to four of the five human somatostatin receptor subtypes (1-3, 5), resulting in inhibition of GLP-1 and insulin secretion, and slows gastric emptying. PASIPHY will evaluate pasireotide efficacy and safety in patients (pts) with PBH. Study design: PASIPHY, a Phase II dose-finding study (NCT05928390), will enroll ∼72 pts with PBH (age ≥18 years; bariatric surgery ≥6 months prior) across ∼25 sites (Europe/USA). The study comprises a ≤3-week (W) screening, a 4W run-in and a 12W randomized, double-blind, placebo-controlled treatment period. Pts with ≥4 postprandial hypoglycemic events (self-monitored blood glucose [SMBG] <54 mg/dL [<3.0 mmol/L], a neuroglycopenia event or a level 3 hypoglycemic event) during the run-in period are randomly allocated to subcutaneous pasireotide at a dose of 50, 100 or 200 μg 3 times a day (tid) or matching placebo (3:1 ratio). All pts initiate treatment with 50 μg tid pasireotide; dose increases will occur on days 5 (to 100 μg tid) and 9 (to 200 μg tid). Those who complete the 12W core phase may choose pasireotide treatment during a 36W open-label extension. All pts will start the extension on pasireotide 50 μg tid; dose can be adjusted for safety/efficacy reasons (up to 200 μg tid). Pts will have continuous glucose monitoring (CGM; blinded in the core phase). The primary endpoint is change in blood glucose levels measured by peak:nadir glucose area under the curve during the mixed-meal tolerance test (MMTT) from baseline to W12 of treatment. Core-phase secondary endpoints (assessed at W4, W8 and W12 of treatment, unless otherwise specified) include: change from baseline in rate of level 2 hypoglycemic events (by SMBG and CGM); proportion of pts with no level 2 hypoglycemic events during a 3-hour MMTT at W12; change from baseline in rate of level 3 hypoglycemic events; change from baseline in frequency of rescue therapy use for level 2/3 hypoglycemic events; change from baseline to W12 in insulin, glucagon and GLP-1 secretion during MMTT; change from baseline to W12 in health-related quality of life; and incidence of adverse events throughout the study. Most of these endpoints and others will also be assessed throughout the extension phase. Conclusions: PASIPHY will yield important data on the efficacy and safety of pasireotide, determining the optimal dose with the best benefit:risk ratio and whether it is a viable treatment option for pts with PBH. Presentation: Saturday, July 12, 2025