General Information

Somatuline is specifically indicated 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.

Somatuline is supplied in strengths of 60 mg, 90 mg and 120 mg designed for subcutaneous injection. The recommended initial dose of the drug in subjects with moderate and severe renal or moderate and severe hepatic impairment is 60 mg at 4 week intervals for 3 months followed by dose adjustment as described below. The recommended initial dose of the drug for all other subjects is 90 mg at 4 week intervals for 3 months. After 3 months the dosage may be adjusted as follows:

GH >1 to = 2.5 ng/mL, IGF-1 normal and clinical symptoms controlled: maintain Somatuline Depot dose at 90 mg every 4 weeks.

GH > 2.5 ng/mL, IGF-1 elevated and/or clinical symptoms uncontrolled, increase Somatuline Depot dose to 120 mg every 4 weeks.

GH = 1 ng/mL, IGF-1 normal and clinical symptoms controlled: reduce Somatuline Depot dose to 60 mg every 4 weeks.

Thereafter the dose should be adjusted according to the response of the patient as measured by reduction in serum GH and /or IGF-1 levels; and/or changes in symptoms of acromegaly.

Clinical Results

FDA Approval
FDA approval of Somatuline Depot was based on the results of two clinical studies.
Study One
This one-year study consisted of 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. All the subjects who had received previous treatment with a somatostatin analog or a dopaminergic agonist were required to undergo a 12-week washout period. In the initial phase, 108 subjects were randomly allocated to receive a single deep subcutaneous injection of Somatuline Depot 60, 90 or 120 mg or placebo. Four weeks later, they entered a fixed dose phase where they received 4 injections of Somatuline Depot; this was completed by 105 subjects. This was followed by a dose-titration phase of 8 injections for a total of 13 injections over 52 weeks (including the placebo phase). Injections were given at 4-week intervals. The dose was titrated twice (every fourth injection), as needed. This phase was completed by 99 subjects. In the double-blind phase of the study, a total of 63% of the lanreotide treated subjects had a > 50% decrease in mean GH from baseline to Week 4 including 52%, 44% and 90% of patients in the 60, 90 and 120 mg groups, respectively, compared to placebo (0%). In the fixed-dose phase at week 16, 72% of all lanreotide-treated subjects had a decrease from baseline in mean GH of > 50% including 68%, 64% and 84% of subjects in the 60, 90 and 120 mg lanreotide treatment groups, respectively. Efficacy achieved in the first 16 weeks was maintained throughout the trial duration.

Study Two
This 48-week, open-label, uncontrolled study enrolled 63 subjects with IGF-1 concentration = 1.3 times the upper limit of normal age range; of whom 57 completed treatment. Any subject who had received prior treatment with a somatostatin analog or dopaminergic agonist underwent a washout period of up to three months. The subjects entered a four-month fixed dose phase where they received four deep 90 mg subcutaneous injections of Somatuline at 4-week intervals. They then entered into a dose-titration phase where the dose of Somatuline was adjusted according to GH and IGF-1 levels at the beginning of the dose titration phase and, if necessary, after another four injections. The subjects were titrated up to the maximum dose of 120 mg and could not titrate down again. After 48 weeks, 43% of the subjects achieved normal age-adjusted IGF-1 concentrations. The mean IGF-1 concentrations after treatment were 1.3 ± 0.7 times the upper limit of normal compared to 2.5 ± 1.1 times the upper limit of normal at baseline. The proportion of subjects with mean GH concentrations of < 2.5 ng/mL increased significantly from 35% to 77% after the fixed-dose phase and 85% at the end of the study. At the end of treatment 38% of the subjects had both normal IGF-1 concentrations and a GH concentration of less than or equal to 2.5 ng/mL and 27% had both normal IGF-1 concentrations and a GH concentration of <1 ng/mL.

Mechanism of Action

Somatuline Depot (lanreotide acetate) is an injectable, sustained-release formulation of lanreotide, an octapeptide somatostatin analog that inhibits Insulin-like growth factor-1 (IGF-1). Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Activity at human SSTR 2 and 5 is the primary mechanism believed responsible for growth hormone inhibition. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine and paracrine functions.

Literature References

Ronchi CL, Boschetti M, Uberti EC, Mariotti S, Grottoli S, Loli P, Lombardi G, Tamburrano G, Arvigo M, Angeletti G, Boscani PF, Beck-Peccoz P, Arosio M; for the Italian Multicenter Autogel Study Group in Acromegaly Efficacy of a slow-release formulation of lanreotide (Autogel 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal study. Clinical Endocrinology 2007 Jun 7

Tomlinson B, Thomas NG, Lan IW, Barbanoj M, Antonijoan RM, Drazna E, Ramis J, Obach R, Peraire C Pharmacokinetic profile of the somatostatin analogue lanreotide in individuals with chronic hepatic insufficiency. Clinical Pharmacokinetics 2006;45(10):1003-11

Caron P, Cogne M, Raingeard I, Bex-Bachellerie V, Kuhn JM Effectiveness and tolerability of 3-year lanreotide Autogel treatment in patients with acromegaly. Clinical Endocrinology 2006 Feb;64(2):209-14

Bronstein M, Musolino N, Jallad R, Cendros JM, Ramis J, Obach R, Leselbaum A, Catus F Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days. Clinical Endocrinology 2005 Nov;63(5):514-9

Gutt B, Bidlingmaier M, Kretschmar K, Dieterle C, Steffin B, Schopohl J Four-year follow-up of acromegalic patients treated with the new long-acting formulation of Lanreotide (Lanreotide Autogel). Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association 2005 Mar;113(3):139-44

Drange MR, Melmed S Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. The Journal of Clinical Endocrinology and Metabolism 1998 Sep;83(9):3104-9.