Endocrine Abstracts

Background: In a phase 3b, open-label study (NCT02354508) assessing efficacy and safety of long-acting pasireotide in patients with uncontrolled acromegaly after ≥3 months of treatment with first-generation SSAs, 18/123 (15%) patients achieved the primary endpoint of mean growth hormone (mGH) <1.0 μg/l and insulin-like growth factor-1 (IGF-1) <ULN (upper limit of normal) at week 36. Here, we present the results from the extension phase of this study.

Methods: Controlled or uncontrolled patients who completed the 36-week core phase were eligible to enter the extension phase (week 36–72). Patients continued on the same pasireotide dose as in the core phase, but uncontrolled patients were allowed additional medication for acromegaly at investigator’s judgement. The primary endpoint was evaluated in the core phase. In the extension phase, the secondary endpoints were the proportion of patients who achieved biochemical control: GH<1 μg/l and IGF-1<ULN, GH<1 μg/l, and IGF-1<ULN (by previous treatment, type of therapy and overall) at weeks 48, 60 and 72, toxicity, laboratory assessments and patient-reported outcomes.

Results: Eighty-eight patients (mean (S.D.) age, 43.7 (11.53) years, mean (S.D.) GH, 11.4 μg/l (25.81), and mean (S.D.) IGF-1, 666.7 μg/l (294.43)) entered the extension phase. Of them, 75 patients (85.2%) completed the additional 36 weeks; 6 patients each discontinued due to unsatisfactory therapeutic effect and physician’s decision, 1 patient withdrew consent. At weeks 36, 48, 60 and 72, 14.8%, 12.5%, 14.8% and 11.4% of patients, respectively, achieved biochemical control. 21.6, 23.9, 21.6 and 20.5% had GH<1 μg/l and 34.1, 33.0, 37.5 and 33.0% had IGF-1<ULN, respectively. Suppressed levels of median GH and mean standardized IGF-1 at extension baseline (2.3 μg/l, 1.6) were maintained at week 48 (1.9, 1.6), week 60 (1.9, 1.5), and week 72 (1.7, 1.5). A higher proportion of patients with lower screening mGH levels (1.0–2.5 μg/l [n=20] vs >2.5 μg/l [n=68]) achieved biochemical control at all 4 time points 55%–65% vs 10.3%–11.8%. During overall study period (N=123), most frequent adverse events suspected to be drug related were hyperglycaemia (41.5%), diabetes mellitus (23.6%) and diarrhoea (11.4%).

Conclusions: In some patients with uncontrolled acromegaly, switching to long-acting pasireotide after ≥3 months of treatment with first-generation SSAs provided biochemical control, which was sustained over continued therapy until 72 weeks. Lower GH screening levels had a favourable impact on the achievement of biochemical control. The long-term safety and tolerability of pasireotide 40 and 60 mg over 72 weeks was consistent with that observed in the first 36 weeks during the core phase.