Long-Acting Pasireotide Provides Clinical Benefit in Patients with Acromegaly: Results from a 30-Month Analysis of the Phase 3 Paola Study
Presentation Number: SUN 432
Date of Presentation: April 2nd, 2017
Mônica R Gadelha*1, Marcello D Bronstein2, Thierry Brue3, Laura De Marinis4, Maria Fleseriu5, Mirtha Guitelman6, Gerald Raverot7, Ilan Shimon8, Juergen Fleck9, Pritam Gupta10, Alberto M Pedroncelli9 and Annamaria Colao11
1Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 2University of São Paulo Medical School, São Paulo, Brazil, 3Hôpital de la Conception, Aix-Marseille University, Centre National de la Recherche Scientifique, and Assistance Publique-Hôpitaux de Marseille, Marseille, France, 4Università Cattolica del Sacro Cuore, Rome, Italy, 5Northwest Pituitary Center, Oregon Health & Science University, Portland, Oregon, 6Hospital Carlos G Durand, Buenos Aires, Argentina, 7Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France, 8Rabin Medical Center, and Sackler School of Medicine, Tel-Aviv University, Petah-Tiqva, Israel, 9Novartis Pharma AG, Basel, Switzerland, 10Novartis Healthcare Private Limited, Hyderabad, India, 11Università Federico II di Napoli, Naples, Italy
Introduction: In the core phase of the PAOLA study, 15.4% & 20.0% of the patients with acromegaly (uncontrolled on first-generation somatostatin analogs) who received pasireotide 40 mg & 60 mg, respectively, achieved biochemical control (growth hormone [GH] < 2.5 µg/L & normalization of insulin-like growth factor 1 [IGF-1]). No patient in the active control arm (long-acting octreotide/lanreotide) achieved biochemical control. Here we report efficacy results at month 30 and safety results from the start of the study till data cutoff (15 Feb, 2015).
Methods: At the end of the core phase (month 6), patients on pasireotide 40/60 mg who achieved biochemical control continued receiving the same dose (double-blind), while patients who were uncontrolled received open-label pasireotide long-acting 60 mg. In the active control arm, patients uncontrolled at month 6 switched to open-label pasireotide 40 mg (crossover arm) and could have the dose increased to 60 mg at extension week 16 if still uncontrolled. The main aim of this extension phase was to collect long-term efficacy (30 months for both pasireotide arms and 24 months for crossover arm) and safety data (reported at data cutoff in patients who received ≥1 dose of pasireotide; from study baseline for both pasireotide arms, and from extension baseline for crossover arm).
Results: 176/198 patients entered the extension phase and 173 patients received ≥1 dose (pasireotide 40 mg, n=57; 60 mg, n=54; crossover, n=62); 106 patients were on treatment at data cutoff. At month 30, in the pasireotide 40 and 60 mg groups, 24.6% (14/57) and 24.1% (13/54) of patients, respectively, achieved biochemical control. At month 30, 31.6% (18/57) and 29.6% (16/54) of patients, respectively, had normal IGF-1 levels; and 40.4% (23/57) and 40.7% (22/54) of patients, respectively, had GH < 2.5 µg/L. Among the patients in the crossover group, at month 30, 32.3% (20/62) achieved biochemical control; 32.3% (20/62) achieved normal IGF-1, and 46.8% (29/62) achieved GH < 2.5 μg/L. The most frequently reported adverse events (AEs) in the pasireotide 40 mg, 60 mg, and the crossover arms were hyperglycemia (39.7%, 40.3%, 22.6%, respectively), diabetes mellitus (25.4%, 32.3%, 27.4%), diarrhea (22.2%, 27.4%, 12.9%) and cholelithiasis (30.2%, 29.0%, 24.2%). In the extension phase, AEs leading to discontinuation occurred in 1 (1.8%), 6 (11.1%), and 6 (9.7%) patients in the pasireotide 40 mg, 60 mg, and crossover arms, respectively.
Conclusion: Response rates for pasireotide at month 30 were similar to those at month 6; GH and IGF-1 levels remained consistently suppressed throughout the extension phase, namely 30 months. The safety profile of pasireotide at data cutoff was similar to that observed at month 6. There were few AE-related discontinuations in the extension phase. Long-term treatment with pasireotide was well tolerated and provided clinical benefit in patients with acromegaly.
Disclosure: MRG: Advisory Group Member, Ionis. TB: Consultant, Pfizer, Inc., Investigator, Novo Nordisk, Speaker, Novo Nordisk, Investigator, Novartis Pharmaceuticals, Advisory Group Member, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Speaker, Merck Serono, Speaker, Strongbridge, Investigator, Ipsen, Speaker, Ipsen, Advisory Group Member, Ipsen, Consultant, Ipsen, Speaker, Pfizer, Inc., Speaker, Sandoz, Investigator, Sandoz. LDM: Study Investigator, Novartis Pharmaceuticals, Consultant, Ipsen, Speaker, Eli Lilly & Company. MF: Study Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Study Investigator, Cortendo, Consultant, Cortendo, Study Investigator, Pfizer, Inc., Consultant, Pfizer, Inc., Study Investigator, Chiasma, Consultant, Chiasma. GR: Consultant, Novartis Pharmaceuticals, Researcher, Novartis Pharmaceuticals, Consultant, Ipsen, Researcher, Ipsen. IS: Advisory Group Member, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals, Consultant, Pfizer, Inc., Researcher, Pfizer, Inc., Speaker, Pfizer, Inc., Consultant, Chiasma. JF: Employee, Novartis Pharmaceuticals. PG: Employee, Novartis Pharmaceuticals. AMP: Employee, Novartis Pharmaceuticals. AC: Advisory Group Member, Novartis Pharmaceuticals, Study Investigator, Novartis Pharmaceuticals. Nothing to Disclose: MDB, MG