Endocrine Abstracts

Background: Pasireotide (Signifor^®), a multireceptor-targeted somatostatin analogue, was initially approved in Europe and the USA in 2012 for treating adult patients with Cushing’s disease for whom surgery is not an option/has failed. This ‘expanded-access’ study allowed patients to receive pasireotide until regulatory approval was obtained in their country, and collected further safety/efficacy data. Here we report an interim analysis of this ongoing study.

Methods: Adult patients with confirmed Cushing’s disease were enrolled; all had mean 24-h UFC>ULN. Patients initiated pasireotide at 600/900 μg sc bid; dose could be increased or decreased in 300 μg increments to a minimum of 300 μg for tolerability issues/sustained UFC normalization, or to a maximum of 900 μg. Patients remain in the study until pasireotide becomes commercially available in their country or 31/12/15, whichever occurs first. The primary objective was to assess the safety of pasireotide; changes in UFC and clinical signs/symptoms in patients with available measurements at weeks 12, 24 and 48 were evaluated as secondary objectives.

Results: As of 31/7/14, 97 patients enrolled (mean age 42.2±12.8 years). Median exposure to pasireotide was 23.6 weeks (range 1–131). 22 patients (22.7%) are still on study and 29 (29.9%) have completed; 46 (47.4%) discontinued: primary reasons were AEs (n=16), unsatisfactory therapeutic effect (n=13), consent withdrawal (n=13) and other (n=4). Most AEs were mild/moderate; most common: nausea (n=48; 49.5%), diarrhoea (n=46; 47.4%), hyperglycaemia (n=38; 39.2%). At weeks 12, 24 and 48: 35/71 (49.3%; 95% CI 37.2–61.4), 24/49 (49.0%; 34.4–63.7) and 11/27 (40.7%; 22.4–61.2) patients had UFC<ULN; 40/71 (56.3%; 44.1–68.1), 26/49 (53.1%; 38.3–67.5) and 11/27 (40.7%; 22.4–61.2) had UFC decrease ≥50% from baseline. Improvements were observed in signs/symptoms, including facial rubor, supraclavicular/dorsal fat pads, striae and bruising.

Conclusions: This study provides further evidence that pasireotide effectively decreases UFC levels and improves clinical signs/symptoms, with a generally favourable safety profile, in patients with Cushing’s disease.

Disclosure: This work was supported by Novartis.