Endocrine Abstracts

JOINT1313

Introduction: B2412 (NCT01794793), an open-label, multicentre, Phase IV rollover study, evaluated the long-term safety of pasireotide (a second-generation, multireceptor-targeted somatostatin receptor ligand) in patients with rare endocrine diseases, including acromegaly and Cushing’s disease (maximum study duration, 10 years). Here, we report data from the final analysis in patients with acromegaly who received pasireotide long-acting release (LAR) during the rollover.

Methods: Patients continuing to receive treatment benefit at the end of a previous pasireotide trial (investigator assessed) were eligible to enter the rollover and initially remained on the same pasireotide dose that they were receiving at the end of the parent study. Data are reported for patients with acromegaly who were treated with pasireotide LAR across five parent studies and received ≥1 pasireotide dose during the rollover. The primary objective of the B2412 study was to evaluate long-term pasireotide safety based on the frequency of adverse events (AEs) and serious AEs (SAEs). Data are reported from rollover start to end, unless otherwise stated.

Results: Overall, 221 patients with acromegaly from 24 countries entered the rollover to receive pasireotide LAR; 75.6% (n = 167) of patients completed treatment and 24.4% (n = 54) discontinued, most commonly because of patient consent withdrawal (5.9%, n = 13). Median (min–max) duration of pasireotide LAR exposure and average dose from parent study baseline to rollover end was 7.5 years (0.3–16.8) and 37.5 mg/month (6–68). AEs regardless of study drug relationship were reported in 77.8% (n = 172) of patients, most commonly (≥10% of patients) hyperglycaemia (12.7%, n = 28), COVID-19, headache (each 10.9%, n = 24) and hypertension (10.4%, n = 23). 65.6% (n = 145) of patients required additional therapy to manage AEs, most commonly for back pain, hypertension (each 9.0%, n = 20) and hyperglycaemia (7.7%, n = 17). 10.9% (n = 24) of patients required dose interruption/adjustment to manage AEs, most commonly for aspartate aminotransferase increased, COVID-19, SARS-CoV-2 test positive, diabetes mellitus, growth hormone deficiency, hyperglycaemia and insulin-like growth factor decreased (each 0.9%, n = 2). SAEs were reported in 22.6% (n = 50) of patients, most commonly COVID-19 (3.2%, n = 7). Three patients died during the rollover (cardiac failure, n = 2; pulmonary embolism, n = 1). Overall, 15 patients (6.8%) discontinued because of AEs, most commonly hyperglycaemia (1.8%, n = 4). No new safety signals were identified.

Conclusion: Pasireotide is a well-tolerated long-term treatment option for patients with acromegaly, with patients having received treatment for ≤17 years from parent study entry. Hyperglycaemia was infrequent, and AEs, including hyperglycaemia, were mostly manageable without treatment discontinuation during the rollover.