Lanreotide Autogel® -: A review of its use in the management of acromegaly

Lanreotide Autogel (R) (ATG) [Somatuline (c) Depot] is a novel, long-acting preparation of the somatostatin analogue lanreotide acetate that acts via somatostatin receptors to reduce both growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. It is indicated for the management of acromegaly and, relative to most other licensed agents, it has a favourable pharmacokinetic profile that permits administration once every 28-42 days. Subcutaneous lanreotide ATG was an effective and generally well tolerated treatment in patients with acromegaly in well designed trials and extension studies of up to 4 years duration. It was shown to be no less effective than intramuscular lanreotide long-acting (LA) microparticles treatment in these studies, with more limited data showing that lanreotide ATG therapy was as effective as intramuscular octreotide long-acting repeating (octreotide LAR) treatment. While both of these latter agents offer the advantage of treatment once every 28 days, lanreotide ATG also has the advantage of being available in a convenient pre-filled syringe and is given subcutaneously rather than intramuscularly like other somatostatin analogues. Thus, it provides a valuable first-line option for the management of patients with acromegaly. Lanreotide acetate has a low affinity for central somatostatin receptors (SSTR-1, SSTR-3 and SSTR-4), and a higher affinity for peripheral somatostatin receptors (SSTR-2 and SSTR-5) in the GH-releasing anterior pituitary and pancreas. This confers a specificity of action at the level of GH release, such that the primary effect of lanreotide is a reduction of GH and thereby IGF-I levels. Lanreotide also has an inhibitory effect on the basal secretion of several gastric enzymes, including motilin, gastric inhibitory peptide and pancreatic polypeptide, and on the postprandial secretion of gastrin and cholecystokinin. In patients with neuroendocrine tumours, lanreotide LA caused tumour shrinkage. Subcutaneous lanreotide ATG (60-120 mg) had a linear pharmacokinetic profile after both single and multiple doses in patients with acromegaly. The maximum mean steady-state concentration of lanreotide was 5.7 mu g/L, which was achieved in a median time of 84 days during a four-dose regimen of lanreotide ATG 90 mg once every 28 days. The release profile of lanreotide was well controlled throughout the whole administration regimen and peak-trough fluctuations were minimal. Owing to the supersaturated nature of the lanreotide ATG preparation, prolonged release of the peptide analogue enables less frequent injections, with a mean half-life of approximate to 22 days. As with other somatostatin analogues, there are some potential drug-drug interactions that should be considered in patients receiving lanreotide ATG. In two prospective, multicentre trials (n = 93 and 107 evaluable patients), subcutaneous lanreotide ATG 60-120 mg once every 28 days provided similar control of GH and IGF-I levels, and overall hormonal control (i.e. GH level <= 2.5 ng/mL and age- and sex-normalized IGF-I levels) in treatment-experienced adult patients with acromegaly who switched from intramuscular lanreotide LA (30 mg every 7-14 days) or octreotide LAR (20-40 mg every 28 days) treatment. Furthermore, fixed dosages of lanreotide ATG for up to 30 weeks were no less effective than lanreotide LA treatment in maintaining GH levels, as determined by prespecified noninferiority boundaries. Overall hormonal control was achieved by approximately one-third of patients during each of these treatment periods. During a 1-year extension study, titrated dosages (based on efficacy) of lanreotide ATG were generally more effective than either 12 weeks of fixed-dose lanreotide ATG treatment or five doses of lanreotide LA treatment. Thus, there were significant improvements in GH and IGF-I levels during titrated lanreotide ATG treatment versus either of the earlier treatment periods, and a greater proportion of titrated lanreotide ATG recipients achieved a mean GH level of <= 2.5 ng/mL and also overall hormonal control. Two small extension studies (n <= 14) of up to 4 years' duration in patients who had participated in the I-year extension study indicated that the benefits of lanreotide ATG treatment were maintained in the long term. With fixed-dose lanreotide ATG treatment, the control of clinical symptoms associated with acromegaly was at least as effective as during lanreotide LA treatment, with clinical symptoms remaining stable during the subsequent 1-year extension phase of lanreotide ATG treatment. Furthermore, in two small (n <= 25), prospective, multicentre studies, the efficacy of lanreotide ATG for up to 42 weeks did not differ from that of prior treatment with intramuscular octreotide LAR (10-40 mg once every 28 days) in reducing GH and IGF-I levels, with approximately half of the patients in each treatment period achieving GH levels of <= 2.5 ng/mL. In these studies, lanreotide ATG was given once every 28 days (60-120 ring titrated doses based on efficacy) or once every 4-8 weeks (120 mg every 6 weeks for 24 weeks, then once every 4, 6 or 8 weeks based on efficacy). Lanreotide ATG treatment was at least as effective as octreotide LAR treatment in controlling the clinical symptoms of acromegaly. Lanreotide ATG for up to 4 years was generally well tolerated in patients with acromegaly. Most adverse events were of mild to moderate intensity, transient and gastrointestinal in nature. The most common adverse events were diarrhoea, cholelithiasis, abdominal pain, nausea, injection-site reactions, constipation, flatulence, vomiting, arthralgia, headache and loose stools in a pooled analysis of 416 patients with acromegaly. Limited data suggest that lanreotide ATG treatment is at least as well tolerated as octreotide LAR treatment.