Lanreotide
BIM 23014, Lanreotide acetate, Lanreotide autogel, Lanreotide depot, Angiopeptin (historical research designation)
Lanreotide is a synthetic octapeptide somatostatin analogue closely related to octreotide, licensed for acromegaly, for the symptoms of carcinoid syndrome, and for slowing progression of gastroenteropancreatic neuroendocrine tumours. Its distinguishing feature is formulation rather than pharmacology: the autogel depot is a self-assembling peptide gel given by deep subcutaneous injection every four weeks.
Mechanism
Lanreotide is an SSTR2-preferring somatostatin receptor agonist with secondary affinity for SSTR5, and negligible activity at SSTR1, SSTR3 and SSTR4. Its receptor pharmacology is close enough to octreotide that the two are generally regarded as interchangeable first-generation analogues, and comparative data in acromegaly show broadly overlapping efficacy. Agonism at SSTR2 couples through Gi to inhibit adenylyl cyclase, reduce cyclic AMP, hyperpolarise the cell through potassium channel opening and close voltage-gated calcium channels, which collectively suppress the regulated secretion of growth hormone from somatotroph adenomas and of serotonin, gastrin, glucagon, insulin and vasoactive intestinal peptide from gastroenteropancreatic neuroendocrine cells.
The antiproliferative arm is described in preclinical work as SSTR2-linked recruitment of SHP-1 and SHP-2 phosphatases, upregulation of the cyclin-dependent kinase inhibitor p27kip1 and consequent G1 cell-cycle arrest, with additional indirect effects on angiogenesis and on insulin-like growth factor signalling within the tumour microenvironment. Structurally, lanreotide differs from octreotide by carrying a D-2-naphthylalanine at position 1 rather than D-phenylalanine, tyrosine in place of phenylalanine at position 3, valine in place of threonine at position 6, and a C-terminal amide instead of an alcohol. The pharmaceutically important feature is not the sequence but the physical chemistry: at high concentration lanreotide acetate self-assembles into nanotubes, forming a viscous gel that releases drug slowly from the injection site without any polymer carrier.
What the research shows
CLARINET is the anchor of the lanreotide evidence base and is one of the cleaner oncology trials of its era: double-blind, placebo-controlled, 204 patients, hazard ratio 0.47 for progression. The important caveats are stated plainly in the paper itself. There was no overall survival benefit and no quality-of-life benefit, the trial enrolled predominantly non-functioning, low-proliferation-index tumours with a majority having stable disease at entry, and the open-label extension in 89 patients that reported median progression-free survival of 38.5 months was uncontrolled. In acromegaly, lanreotide autogel produces biochemical control rates broadly comparable with octreotide LAR, in the region of 50-65% depending on how control is defined and whether patients are treatment-naive.
Where lanreotide underperforms expectations is symptomatic carcinoid syndrome. ELECT met its primary endpoint but the absolute difference was 14.8 percentage points of rescue-medication days, and patients on active drug still needed rescue octreotide on a third of days. Direct comparisons between lanreotide autogel and octreotide LAR have generally not shown clinically important differences, so the choice between them in practice usually turns on injection route, injection-site tolerability and whether a patient or carer can administer it at home. The most frequently cited evidence of a difference, the 2000 switch study, does not support the weight often placed on it.
Evidence assessment
High-quality evidence
CLARINET was an adequately powered, double-blind, placebo-controlled phase 3 trial in 204 patients with a progression-free survival endpoint, followed by an open-label extension in 89 patients; ELECT provided randomised placebo-controlled evidence for carcinoid syndrome symptom control in 115 patients. Lanreotide carries approved labelling from the FDA and from European regulators including the MHRA across three indications. This meets the strict definition of strong evidence. The qualifier that belongs alongside it: CLARINET showed no overall survival and no quality-of-life benefit, and the ELECT effect size was modest.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Lanreotide in metastatic enteropancreatic neuroendocrine tumors Preclinical only
Median progression-free survival was not reached in the lanreotide arm versus 18.0 months on placebo (hazard ratio 0.47). Progression-free survival at 24 months was 65.1% versus 33.0%. There was no significant difference in overall survival or quality of life, and diarrhoea was more frequent with lanreotide. Most patients had stable disease at entry, so this is a trial of maintaining stability rather than of reversing progression.
Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study Preclinical only
Median progression-free survival in the group receiving lanreotide in both the core study and the extension was 38.5 months (95% CI 30.9 to 59.4), with median exposure of 59.0 months. Overall incidences of adverse events and treatment-related adverse events were lower during the extension than in the core study. In placebo-treated patients who had progressed by the end of the core study, time to death or subsequent progression during the extension was 19 months. This is an uncontrolled extension, so the progression-free survival figure carries none of the causal weight of the randomised core trial.
Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrome treatment (ELECT): a randomized, double-blind, placebo-controlled trial Preclinical only
The adjusted mean percentage of days requiring rescue octreotide was 33.7% (95% CI 25.0-42.4) with lanreotide versus 48.5% (39.6-57.4) with placebo, an absolute difference of -14.8% (95% CI -26.8 to -2.8, P=0.017). The odds ratio for full or partial treatment success was 2.4 (1.1-5.3, P=0.036). A statistically clear but numerically modest effect: patients on active drug still needed rescue medication on a third of days.
Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly Preclinical only
Biochemical control improved after the switch (normal IGF-I 48% to 65%) and the authors concluded octreotide LAR was more effective than lanreotide SR. Interpretation requires real care, and more than the draft allowed. This is a within-patient switch study, not a parallel-group head-to-head trial, so order effects are uncontrolled; the comparator was the older sustained-release lanreotide formulation given every 10-14 days, not the modern autogel; and later studies with autogel have not reproduced a clear disadvantage for lanreotide. Included because it is frequently cited as evidence of a difference between the two analogues that subsequent formulations and better-controlled designs largely erased.
Safety
The adverse effect profile mirrors octreotide almost exactly, because the receptor pharmacology is nearly identical. Gastrointestinal effects dominate: diarrhoea, abdominal pain, flatulence and nausea, most prominent in the first weeks, and diarrhoea was more frequent than placebo in CLARINET. Cholelithiasis and biliary sludge are the characteristic long-term risk, driven by suppression of cholecystokinin-mediated gallbladder emptying, and ultrasound surveillance is standard. Injection-site reactions, including nodules, pain and induration, are prominent because the autogel is a viscous deep subcutaneous injection.
Glucose handling can shift in either direction through combined suppression of insulin, glucagon and growth hormone, and monitoring is required, particularly in patients with pre-existing diabetes. Sinus bradycardia occurs and matters in patients on rate-limiting drugs. Rarer effects include pancreatitis, hypothyroidism and elevated hepatic transaminases. Fat malabsorption with long-term use can produce deficiency of fat-soluble vitamins and of vitamin B12. Lanreotide is a specialist-initiated prescription medicine requiring structured biochemical, imaging and gallbladder monitoring; it is not suitable for unsupervised use.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | Licensed by the MHRA for acromegaly, for the relief of symptoms associated with neuroendocrine (particularly carcinoid) tumours, and for the treatment of grade 1 and a subset of grade 2 gastroenteropancreatic neuroendocrine tumours (Ki-67 index up to 10%) of midgut, pancreatic or unknown origin where hindgut sites of origin have been excluded, in adults with unresectable locally advanced or metastatic disease. Corrected during audit: the draft stated a licensed criterion of 'hepatic tumour load of 25% or less', which is not part of the marketing authorisation; hepatic tumour load was a CLARINET trial stratification variable, not a licensing restriction. The draft's claim about a NICE appraisal could not be verified in this audit and has been removed. Prescription-only, specialist-initiated. |
| United States | Approved by the FDA in 2007 for acromegaly, in December 2014 for unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours to improve progression-free survival, and in 2017 for carcinoid syndrome. Prescription-only. |
| WADA (sport) | Not prohibited on the current Prohibited List. Like other somatostatin analogues it suppresses growth hormone secretion rather than stimulating it, so it falls outside S2.2, and it does not appear in any other category. The List is revised annually. |
Questions
For most purposes, no. The two are first-generation SSTR2-preferring analogues with very similar receptor profiles, and comparative data in acromegaly show broadly comparable biochemical control. The one study most often cited as showing octreotide is superior was a within-patient switch study against an older lanreotide formulation, which is a weak basis for the claim. The practical differences are formulation-related: lanreotide autogel is a deep subcutaneous injection that some patients or carers can be trained to administer, while octreotide LAR is an intramuscular depot usually given in clinic.
Most depot injections rely on a polymer carrier such as poly(lactide-co-glycolide) microspheres to slow release. Lanreotide autogel has no carrier at all. At high concentration the peptide self-assembles into nanotubes that form a viscous gel, and the drug releases as that gel gradually disperses. Elimination is therefore limited by absorption rather than clearance, giving an apparent half-life of several weeks.
No. CLARINET showed a delay in progression, not tumour eradication, and objective tumour shrinkage was uncommon. There was no demonstrated overall survival benefit in the trial, and no quality-of-life benefit. The realistic goal is disease stabilisation over a period of years in an indolent malignancy, which is valuable but should not be described as cure.
No. It suppresses growth hormone rather than releasing it, which puts it outside the S2.2 growth hormone secretagogue category, and it appears nowhere else on the current List. The List is revised annually, and as with any prescription medicine athletes should declare it during doping control.