Endocrine Abstracts (2016) 46 OC1 | DOI: 10.1530/endoabs.46.OC1

Netazepide, a gastrin/CCK2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis

Malcolm Boyce1, Andrew Moore2, Bryony Parsons2, Katie Lloyd2, Liv Sagatun3, Liv Thomsen1, Andrea Varro2, Reidar Fossmark3, Helge Waldum3 & David M Pritchard2

1Hammersmith Medicines Research, London, UK; 2Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; 3Departments of Gastroenterology and Pathology, St. Olav’s Hospital, and the Departments of Cancer Research, Molecular Medicine and Laboratory Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Introduction: In a two-centre, 12-week, open trial in 16 patients with autoimmune chronic atrophic gastritis, hypergastrinaemia, multiple type 1 gastric neuroendocrine tumours (NETs), and raised circulating CgA, the gastrin/CCK2 receptor antagonist (CCK2RA), netazepide, reduced the tumour number and size, and normalised CgA.

Aim(s): To treat those patients with netazepide for longer, and to identify new biomarkers.

Materials and methods: After a mean 14 months off netazepide, 13 patients took it for another 52 weeks. Assessments were: gastroscopy; gene transcript expression in corpus biopsies; and blood CgA, miR-222 and gastrin.

Results: While off treatment, the number and size of the tumours, and CgA all increased again. Netazepide for 52 weeks eradicated all tumours in 5 patients, left one patient with only one tumour, and reduced further the number and size of the tumours in the others, and normalised CgA (P<0.01). Gastrin was unaffected. Netazepide was safe and well tolerated.

Netazepide reduced mRNA abundances of overexpressed CgA, histidine decarboxylase, pappalysin 2 (PAPPA2), glycoprotein hormones alpha polypeptide, and miR-222 in biopsies, and miR-222 in blood (P<0.05). miR-222 targets the tumour suppressor and oncogene p27kip1.

Conclusions: A CCK2RA is a potential medical and targeted treatment for gastric NETs that are gastrin driven, and an alternative to endoscopic resection or surgery. Treatment can be monitored by biomarkers in blood or biopsies. The results justify a multicentre, placebo-controlled trial.