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

FDA has approved Somatuline Depot, an analog of natural somatostatin, 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.