THU066 An 8-year Interim Report Of The B2412 Study, An Open-label, Multicenter Pasireotide Rollover Study For Patients Who Continued To Receive Benefit From Pasireotide At Completion Of An Earlier Trial
Authors: Gadelha Mônica , Bronstein Marcello Delano , Grineva Elena , Kapoor Nitin , De Block Christophe , Escalante Pulido Jesus Miguel , Rollin Guilherme , Baggenstoss Rejane , Piacentini Andrea , Pedroncelli Alberto M , Gallardo Wilson 
Published: October 2023

Abstract
Disclosure: M. Gadelha: Advisory Board Member; Self; Novo Nordisk, Recordati, Crinetics Pharmaceuticals. Speaker; Self; Recordati, Novo Nordisk, Ipsen, Crinetics Pharmaceuticals. M.D. Bronstein: None. E. Grineva: Advisory Board Member; Self; Ipsen, Merck, Pfizer, Inc. Speaker; Self; Recordati, Ipsen, Pfizer Berlin Chemie, Teva Pharmaceutical Industries Ltd., A. Menarini, Siemens Healthineers. N. Kapoor: None. C. De Block: Consulting Fee; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly & Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Indigo Diabetes, Novo Nordisk. Speaker; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly & Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. J.M. Escalante Pulido: None. G. Rollin: Advisory Board Member; Self; Merck Serono. Speaker; Self; Novo Nordisk, Abbott Laboratories, AstraZeneca, Merck Serono. R. Baggenstoss: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. W. Gallardo: Speaker; Self; Pfizer, Inc., Merck, Ipsen, Novartis Pharmaceuticals.
Introduction: A robust clinical development program of 14 trials demonstrated that the second-generation somatostatin receptor ligand, pasireotide, is an effective treatment for patients (pts) with rare endocrine disorders, including acromegaly and Cushing’s disease (CD). Pts with acromegaly or CD have significant morbidity, reduced quality of life and, if inadequately treated, a higher mortality risk than the general population. This 8-year interim analysis evaluated the long-term safety of pasireotide treatment in pts with acromegaly, CD or other endocrine disorders. Methods: This ongoing, open-label, multicenter study allows continued treatment for pts who completed a previous pasireotide parent trial (NCT01794793). Pts who continued to receive clinical benefit, as determined by the investigator in the parent study, entered the rollover study and remained on pasireotide. Depending on the route of administration in the parent study, pts received pasireotide long-acting release (LAR; n=303) or subcutaneous (sc; n=38) as monotherapy (n=36), or sc in combination with cabergoline (n=2). The primary objective was to evaluate long-term safety, determined by frequency of adverse events (AEs)/serious adverse events (SAEs). Results: Overall, 341 pts from 29 countries have entered the study from 14 parent studies; 228 pts had acromegaly, 64 CD and 49 other endocrine disorders, including melanoma, dumping syndrome and neuroendocrine tumors. Median (min−max) exposure to all pasireotide formulations from rollover baseline to data cut-off and across all indications was 45.3 months (0.9−100.8). Median (min−max) dose from rollover baseline was 45.4 mg/month (5.3−128.3) with pasireotide LAR and 1200 µg/day (300−1800) with pasireotide sc. In total, 89 (26.1%) pts discontinued treatment; the most common reason was consent withdrawal (n=21, 6.2%). Most common AEs during rollover (≥10% in all pts) were nasopharyngitis (acromegaly n=13, 5.7%; CD n=14, 21.9%; other diseases n=14, 28.6%), hyperglycemia (acromegaly n=29, 12.7%; CD n=2, 3.1%; other diseases n=7, 14.3%), back pain (acromegaly n=20, 8.8%; CD n=7, 10.9%; other diseases n=8, 16.3%) and headache (acromegaly n=21, 9.2%; CD n=6, 9.4%; other diseases n=7, 14.3%). SAEs were reported in 87 (25.5%) pts; the most common were cholelithiasis and COVID-19 (both n=9, 2.6%). Overall, 18 (5.3%) pts discontinued treatment because of AEs. Incidence of new hyperglycemia-related AEs during rollover was low. No new safety signals were identified. Conclusions: Hyperglycemia is an expected AE during pasireotide treatment, often occurring in the first 3 months of therapy. These data in pts with acromegaly, CD or other endocrine disorders support pasireotide as a well-tolerated long-term treatment and affirm that pts continue to receive long-term benefit, with a low discontinuation rate over 8 years.
Presentation: Thursday, June 15, 2023