Endocrine Abstracts

Introduction: Acromegaly is associated with significant morbidity and reduced quality of life. A robust clinical programme (14 trials) established pasireotide as an effective second-generation somatostatin receptor ligand for the treatment of various endocrine conditions, including acromegaly. Patients who completed a previous pasireotide trial and continued to receive clinical benefit, according to the parent study investigator, could continue treatment in the B2412 rollover study, which assessed long-term safety and clinical benefit.

Methods: This ongoing, open-label, multicentre, Phase IV study allows continued treatment for patients with acromegaly, Cushing’s disease or other endocrine disorders who completed a pasireotide parent trial (NCT01794793). Here, we analysed patients with acromegaly who received pasireotide LAR in four parent studies (B2219, C2305, C2402, C2413) and ≥1 dose during the rollover, including cumulative data from parent study baseline to rollover interim data cut-off (1 November 2021). The B2412 study primary objective was to evaluate long-term safety, determined by adverse event (AE)/serious adverse event (SAE) frequency.

Results: Overall, 211 patients from 23 countries entered the rollover from four parent studies. At data cut-off, 59.2% of patients (n=125) were continuing treatment, 24.2% (n=51) had completed the study and 16.6% (n=35) had discontinued the study. The most common reason for study discontinuation was AEs (n=12; 5.7%). Median (min−max) exposure from first dose in the parent study to rollover data cut-off was 64.0 months (9–148), with a median (min−max) average dose of 44.8 mg/month (6–69). The most common AEs considered by the investigator to be treatment related from the first dose in the parent study to rollover data cut-off (≥10% of patients) were hyperglycaemia (34.1%), cholelithiasis (25.6%), diabetes mellitus (not further specified; 25.1%) and diarrhoea (16.6%). The most common AE leading to treatment discontinuation was hyperglycaemia (1.9%). AEs that most frequently required additional therapy (≥20% of patients) were hyperglycaemia (28.9%) and diabetes mellitus (not further specified; 26.5%). SAEs were reported by 29.4% of patients (n=62), most commonly cholelithiasis (6.2%) and COVID-19 (3.3%); all other SAEs were reported with <1% frequency. Altogether, >94% of patients were assessed as deriving clinical benefit from pasireotide LAR treatment at all study visits.

Conclusions: Pasireotide is well tolerated and provides clinical benefit for up to 12 years of treatment in patients with acromegaly. Hyperglycaemia, an AE often reported during the first 3 months of pasireotide treatment, is manageable, usually without the need for treatment discontinuation.