A sustained-release formulation of the somatostatin analogue lanreotide has been approved by the Food and Drug Administration for the long-term treatment of acromegaly patients who have had an inadequate response to or cannot be treated with surgery or radiotherapy.
Lanreotide is administered via a deep subcutaneous injection every 4 weeks for 3 months, after which time the dosage is adjusted based on the patient's response, which is determined by a reduction in serum growth hormone or insulin growth factor-1 (IGF-1) levels, as well as changes in symptoms of acromegaly, according to the labeling.
In the United States, the prolonged-release formulation of lanreotide, which the label says is a synthetic octapeptide with a biological activity similar to naturally occurring somatostatin, is being marketed as Somatuline Depot.
The label cites two long-term, randomized multicenter studies of different doses of Somatuline Depot in patients with acromegaly. In a 1-year study, 108 patients with active acromegaly were randomized to receive a 60-mg, 90-mg, or 120-mg injection of lanreotide or placebo, after which all patients received a fixed dose every 4 weeks for 4 months (4 injections), followed by a dose-titration phase of 8 injections for a total of 13 injections over 12 months. At the end of the first month, 63% of the patients treated with lanreotide had more than a 50% drop in mean growth hormone (GH) levels from baseline, compared with none of the 25 patients on placebo. At week 16, the end of the fixed dose phase, 72% of the lanreotide-treated patients had more than a 50% reduction in mean GH level, which was maintained for the rest of the study.
The second study described in the label was a 48-week, open-label, uncontrolled study of 63 patients with an IGF-1 level that was at least 1.3 times the upper limit of the age-adjusted normal range. During a 4-month fixed-dose phase, patients received four injections of 90 mg of Somatuline Depot every 4 weeks. This was followed by a dose-titration phase, during which the dose was adjusted based on GH and IGF-1 levels at the beginning of this phase, and again, if needed, after patients received another four injections. After 48 weeks, 43% of the patients achieved a normal age-adjusted IGF-1 concentration. The mean IGF-1 concentration after treatment was 1.3 ± 0.7 times the upper limit of normal, compared with 2.5 ± the upper limit of normal at baseline. The drop in IGF-1 levels “over time correlated with a corresponding marked decrease in GH concentrations,” according to the label, which cited the most common adverse reactions associated with treatment as diarrhea, cholelithiasis, abdominal pain, nausea, and injection site reactions.
Somatuline Depot, which has been available in Europe for a while, will be “a useful addition to our formularies,” Dr. Rhoda H. Cobin of Mount Sinai School of Medicine, New York, said in an interview. It is a longer-acting version of octreotide, used in the United States, which makes administration easier and will help with patient compliance, said Dr. Cobin, the immediate past president of the American College of Endocrinology and past president of the American Association of Clinical Endocrinologists.
Somatuline Depot is manufactured by Ipsen. Tercica, has the U.S. distribution rights and expects to launch the drug in the fourth quarter of 2007, according to Ipsen.
It is a longer-acting version of octreotide, making its administration easier and helping with patient compliance. DR. COBIN