Sustained biochemical control in patients with acromegaly treated with lanreotide depot 120 mg administered every 4 weeks, or an extended dosing interval of 6 or 8 weeks: a pharmacokinetic approach

Abstract

Sustained biochemical control in patients with acromegaly treated with lanreotide depot 120 mg administered every 4 weeks, or an extended dosing interval of 6 or 8 weeks: a pharmacokinetic approach Edda Gomez-Panzani,1 Stephen Chang,1 Joaquim Ramis,2 Michelle M Landolfi,1 Bert Bakker11Ipsen Biopharmaceuticals, Inc, Basking Ridge, New Jersey, USA; 2Ipsen Innovation SAS, Pharmacokinetic and Drug Metabolism, Les Ulis, FranceObjective: Lanreotide depot is a long-acting somatostatin receptor ligand injected deep subcutaneously every 4 weeks for the treatment of acromegaly. The aim of the presented studies was to establish whether lanreotide depot, administered to patients with acromegaly at an extended dosing interval of 6 or 8 weeks, is effective in maintaining appropriate serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, with acceptable tolerability.Methods: Two studies were conducted. Study B1 compared lanreotide depot 120 mg (every 4, 6, or 8 weeks) with lanreotide microparticle formulation 30 mg (every 7, 10, or 14 days) in 98 patients who had a GH level of ≤2.5 ng/mL and normalized IGF-1. Study B2 evaluated lanreotide depot 120 mg administered to 64 patients every 8 weeks, after which the dosing interval was adjusted based on GH levels.Results: Mean lanreotide trough serum concentrations at steady state for all dosing intervals were >1.13 ng/mL, shown to achieve a GH level of ≤2.5 ng/mL. In Study B1, following treatment with lanreotide depot given every 6 or 8 weeks, 87.5% and 93.9% of patients, respectively, had normalized GH, whereas 83.3% and 88.5% of patients, respectively, had both normalized GH and IGF-1. In Study B2, 88.9% had normalized GH and 42.9% of patients had normalized GH and IGF-1 following lanreotide depot every 8 weeks. Gastrointestinal disorders, generally mild/moderate in severity, were the most common adverse events.Conclusion: In the studies presented, lanreotide depot 120 mg every 4, 6, or 8 weeks provided effective hormonal control with acceptable safety. An extended dosing interval is a feasible approach for patients adequately controlled with lanreotide depot 60 or 90 mg every 4 weeks.Keywords: growth hormone, insulin-like growth factor-1, pharmacokinetics, pharmacodynamics