ECE2016 Eposter Presentations Pituitary - Clinical (83 abstracts)
Long-term (19-month) control of urinary free cortisol with osilodrostat in patients with Cushing’s disease: results from an extension to the LINC-2 study
Rosario Pivonello 1 , Betul Hatipoglu 2 , Xavier Bertagna 3 , Maria Fleseriu 2 , Mark E Molitch 4 , Chikara Shimizu 5 , Tomoaki Tanaka 6 , Akira Shimatsu 7 , Beverly M K Biller 8 , Shoba Ravichandran 9 , Albert Kandra 10 , Nicholas Sauter 9 & Jacques Young 11
1Università Federico II di Napoli, Naples, Italy; 2Cleveland Clinic, Cleveland, Ohio, USA; 3Hôpital Cochin, Université Paris 5, Paris, France; 4Northwestern University, Chicago, Illinois, USA; 5Hokkaido University Hospital, Sapporo, Japan; 6Chiba University Hospital, Chiba-city, Japan; 7National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 8Massachusetts General Hospital, Boston, Massachusetts, USA; 9Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 10Novartis Pharma AG, Basel, Switzerland; 11Hôpital Bicêtre, Université Paris-Sud, Assistance Publique Hôpitaux de Paris, Paris, France.
Introduction: During the 22-week LINC-2 study, the potent oral 11β-hydroxylase inhibitor osilodrostat normalized UFC in 15/19 (78.9%) patients with Cushing’s disease. Most common AEs were nausea, diarrhoea, asthenia, and adrenal insufficiency. This report describes 19-month results following an extension.
Methods: Patients who were receiving clinical benefit at week 22 could enter the extension. Efficacy/safety is reported for patients who entered the extension. Response was assessed exploratively by last-observation-carried-forward analysis for ongoing patients at the specific time point. AEs are reported from core baseline until last patient reached month 19 (maximum follow-up=27.5 months).
Results: 16/17 patients (male:female=5:11) who completed the core entered the extension. Response rate (UFC≤ULN [control] or UFC>ULN but >50% decrease from baseline [partial control]) for these patients was 94% at week 22 (control: 94% [n=15/16]; partial control: 0% [n=0/16]) and month 19 (control: 81% [n=13/16]; partial control: 13% [n=2/16]). No controlled patients experienced ‘escape’ (UFC>ULN at ≥2 consecutive visits on maximum tolerated dose) during the extension. Blood pressure, weight/BMI remained stable throughout treatment. In patients with diabetes history (n=3), mean±S.D. FPG, HbA1c decreased by 60.7±39.3 mg/dl, 1.1±0.6% from baseline to month 19. Two patients discontinued during the extension (AEs [increased ACTH (maximum=1493 pmol/l), pituitary-tumour enlargement], n=1; consent withdrawal, n=1), one of whom after month 19. Most common AEs were increased ACTH (n=7), adrenal insufficiency, diarrhoea, and nasopharyngitis (n=6). In females, increases in mean±S.D. testosterone from baseline were 2.7±3.4 nmol/l at week 22 (n=10), 0.8±1.3 nmol/l at month 19 (n=9). Hirsutism was reported in one female and acne in two, which emerged before week 22. One patient experienced QTc prolongation >450 ms during the extension (494 ms), which was reversible on dose reduction.
Conclusions: UFC normalization was maintained for 19 months of osilodrostat treatment in 81% of patients with Cushing’s disease. The long-term safety profile of osilodrostat was similar to that reported after 22 weeks.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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