Long-term safety and efficacy of subcutaneous pasireotide in patients with cushing

Fausto Bogazzi; Salvatore Cannavo; Carla Giordano; Mario Detomas; Carla Scaroni; Gerald Raverot; Jochen Schopohl; Carmen Georgescu; Andrea Piacentini; Arnd Mueller; Julia Stermenska; Jerome Bertherat

doi:10.1530/endoabs.99.EP270

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Endocrine Abstracts (2024) 99 EP270 | DOI: 10.1530/endoabs.99.EP270

ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)

Long-term safety and efficacy of subcutaneous pasireotide in patients with cushing’s disease: results from a non-interventional study

Fausto Bogazzi ¹ , Salvatore Cannavò ² , Carla Giordano ³ , Mario Detomas ⁴ , Carla Scaroni ⁵ , Gérald Raverot ⁶ , Jochen Schopohl ⁷ , Carmen Georgescu ⁸ , Andrea Piacentini ⁹ , Arnd Mueller ¹⁰ , Julia Stermenska ¹⁰ & Jérôme Bertherat ¹¹

Err

Author affiliations

¹University of Pisa, Endocrinology United Department of Clinical and Experimental Medicine, Pisa, Italy; ²University Hospital of Messina, Unit of Endocrinology, Messina, Italy; ³University of Palermo, Section of Endocrinology, Dipartimento Biomedico di Medicina Interna e Specialistica (DiBiMiS), Palermo, Italy; ⁴University Hospital Würzburg, Department of Internal Medicine, Division of Endocrinology and Diabetes, Würzburg, Germany; ⁵Hospital-University of Padova, Endocrinology United Department of Medicine, DIMED, Padova, Italy; ⁶Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France; ⁷Klinikum der Universität München, Medizinische Klinik IV, Munich, Germany; ⁸Cluj County Emergency Hospital and Iuliu Hatieganu University of Medicine and Pharmacy, Endocrinology Clinical United, Cluj-Napoca, Romania; ⁹Recordati SpA, Milan, Italy; ¹⁰Recordati AG, Basel, Switzerland; ¹¹Hôpital Cochin, AP-HP, and Université de Paris Cité, Centre de Référence des Maladies Rares de la Surrénale, Paris, France

Introduction: Subcutaneous (sc) pasireotide effectively reduces cortisol levels and is generally well tolerated in Cushing’s disease (CD) patients, as demonstrated by a Phase III study (NCT00434148). We report data from a non-interventional, multinational study (NCT02310269) evaluating long-term safety and efficacy of pasireotide sc for CD patients.

Methods: Adults with CD, for whom surgery has failed or is not an option, were analysed by time of pasireotide sc initiation (at study entry: ‘new-use’ [NU] patients; before study entry: ‘prior-use’ [PU] patients) and monitored for 3 years. The primary endpoint was incidence of pasireotide-related adverse events (AEs) and serious AEs (SAEs). A key secondary endpoint was the proportion of patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) over time.

Results: The full analysis set (FAS) included 152 patients (45 NU, 107 PU); the safety set (SS) included 148 patients (43 NU, 105 PU). In the SS, median (min–max) pasireotide sc exposure was: NU, 7 (0–37) months on study; PU, 34 (0–132) months from drug initiation. 50/105 (48%) PU patients received pasireotide sc for >36 months. Median (min–max) dose on study (n=148) was 1200 (300–1800) μg/day. Pasireotide-related AEs occurred in 59.5% (n=88/148) of SS patients (NU, 79.1% [n=34/43]; PU, 51.4% [n=54/105]), mostly (>15%) nausea (16.9% [n=25/148]). Hyperglycaemia occurred in 10.1% (n=15/148) of SS patients (NU, 23.3% [n=10/43]; PU, 4.8% [n=5/105]). Pasireotide-related SAEs occurred in 16.2% (n=24/148) of SS patients (NU, 25.6% [n=11/43]; PU, 12.4% [n=13/105]), mostly (>2.5%) hyperglycaemia (3.4% [n=5/148]). The only reported grade 4 pasireotide-related SAE was hyperglycaemia (NU, n=1). The proportion of patients who discontinued because of pasireotide-related AEs and SAEs were 23.6% (n=35/148; NU, 32.6% [n=14/43]; PU, 20.0% [n=21/105]) and 6.1% (n=9/148; NU, 9.3% [n=4/43]; PU, 4.8% [n=5/105]), respectively. The proportion of patients (FAS) with mUFC ≤ULN (138 nmol/24 h) at baseline and months 12, 24 and 36 were: NU, n=4/23 (17.4%), n=3/10 (30.0%), n=5/7 (71.4%), n=1/3; PU, n=30/45 (66.7%), n=31/41 (75.6%), n=24/36 (66.7%), n=9/15 (60.0%).

Conclusions: Pasireotide-related AEs and SAEs, including hyperglycaemia, occurred more frequently in NU than PU patients. This suggests that most AEs, including hyperglycaemia, typically occur in the early stages after pasireotide sc initiation and can be effectively managed long term. Most patients achieved/maintained cortisol control over 36 months. Pasireotide sc has a manageable safety profile and is effective for the long-term treatment of CD patients.