Somatuline Depot: New molecular entity recently approved by FDA for the treatment of acromegaly

Key Points

IPSEN

This synthetic octapeptide analog of natural somatostatin has a high affinity for human somatostatin receptors 2 and 5; activity at these receptors is believed to be the primary mechanism responsible for growth hormone (GH) inhibition. This agent was approved on August 30, 2007, for the long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.

Efficacy. The efficacy of lanreotide was assessed in 2 long-term, multiple-dose, randomized, multicenter studies. Study 1 was a 1-year trial that included a 4-week, double-blind, placebo-controlled phase; a 16-week, single-blind, fixed-dose phase; and a 32-week, open-label, dose-titration phase. Patients with active acromegaly (N=108) were randomized to receive a single deep subcutaneous (SC) injection of lanreotide 60, 90, or 120 mg or placebo. After 4 weeks, patients entered the fixed-dose phase, during which they received 4 injections of lanreotide, followed by a dose-titration phase of 8 injections (administered at 4-wk intervals), for a total of 13 injections over 52 weeks. The dose was titrated twice as needed during the dose-titration phase. In the double-blind phase of the study, 63% of the lanreotide-treated patients experienced a >50% decrease in mean GH from baseline to Week 4 versus 0 patients treated with placebo. During the fixed-dose phase, 72% of all 107 lanreotide-treated patients had a decrease in mean GH of >50% from baseline to Week 16. Efficacy was maintained throughout the study. Study 2 was a 48-week, open-label, uncontrolled, multicenter study that enrolled patients with an insulin growth factor-1 (IGF-1) concentration ≥1.3 times the upper limit of the age-adjusted normal range. Eligible patients (N=63) received 4 deep SC injections of lanreotide 90 mg at 4-week intervals for 4 months (fixed-dose phase). Patients then entered a dose-titration phase, during which the lanreotide dose was adjusted based on GH and IGF-1 levels at the beginning of the study phase and again, as needed, after an additional 4 injections. After 48 weeks of lanreotide treatment, 43% of patients had achieved normal age-adjusted IGF-1 concentrations. Additionally, the proportion of patients with mean GH concentrations <2.5 ng/mL increased significantly, from 35% at baseline to 77% after the fixed-dose phase and to 85% by study end.

Dosing. Lanreotide should be initiated at a dose of 90 mg (administered via the deep SC route) at 4-week intervals for 3 months. After 3 months, dosage may be adjusted based on GH levels, IGF-1 levels, and symptoms: for patients with GH >1 to 2.5 ng/mL, normal IGF-1, and controlled clinical symptoms, lanreotide treatment should be maintained at a dose of 90 mg every 4 weeks. For patients with GH >2.5 ng/mL, elevated IGF-1, and/or uncontrolled symptoms, the dose should be increased to 120 mg every 4 weeks. For patients with GH ≤1 ng/mL, normal IGF-1, and controlled symptoms, the dose should be reduced to 60 mg every 4 weeks. Doses may then be adjusted according to patient response.