Gastrin 17 vaccine--Aphton: Anti-gastrin 17 immunogen, G17DT.

Abstract

Aphton is developing an anti-gastrin vaccine [Anti-gastrin 17 immunogen, G17DT, Gastrimmune], which neutralises the gastrin 17 hormone and the Gly-G17 hormone. Gastrin 17 is a growth factor for pancreatic, stomach and colorectal cancers, and a potent stimulator of gastric acid secretion.The anti-gastrin immunogen, G17DT, consists of a large carrier protein, called Diptheria Toxoid (DT). A synthetic peptide, which is similar to a portion of the gastrin 17 hormone (GT), is attached to the carrier protein. These are then contained in a liquid suspension vehicle. When administered to patients, G17DT induces an immune response producing antibodies, which cross-react and neutralise the target hormone thus preventing its interaction with disease-causing or -participating cells. Aphton has entered into an agreement with Aventis Pasteur for the marketing of G17DT in all human cancer indications in North America and Europe. Under the terms of the agreement, Aphton is responsible for product development, clinical trials and regulatory agency approvals. The agreement was originally with Pasteur Mérieux Connaught, a subsidiary of Rhône-Poulenc. However, in December 1999, Rhône-Poulenc merged with Hoechst to form Aventis. As a result of the merger, Pasteur Mérieux Connaught underwent a name change to Aventis Pasteur. In July 2002, Aphton announced that it would negotiate with companies wanting to licence the vaccine in territories other than North America and Europe. In February 2003, Aphton announced it had received fast track designation for G17DT in combination with cisplatin and fluorouracil for use in stage IV gastric cancer to improve overall survival. In July 2002, the US FDA granted G17DT orphan drug status for the treatment of gastric cancer, an indication that was broader than the indication Aphton originally sought. The vaccine was also granted orphan drug status in Australia for gastric cancer in December 2002. In July 2002, Aphton announced that the US FDA had granted G17DT orphan drug status for the treatment of adenocarcinoma of the pancreas. In September 2002, the US FDA also granted G17DT, used in combination with gemcitabine, fast track status for the treatment of pancreatic cancer patients. In addition, the vaccine was also granted orphan drug status in Australia for pancreatic cancer in December 2002. In March 2003, Aphton announced that the Committee for Orphan Medicinal Products had recommended to the European Commission that G17DT be granted orphan drug status for both pancreatic and gastric cancer in the EU. Aphton expects this will be approved and ratified within a few weeks. In August 2002, Aphton filed an IND with the US FDA, as well as the European equivalent, to conduct clinical trials for patients suffering from gastro-esophophageal reflux disease (GERD). The trials will assess, among other endpoints, the efficacy of G17DT in providing symptomatic relief to patients with GERD. In November 2002, Aphton announced that it had received approval to initiate a clinical trial in Europe. Additionally, Aphton has agreed with the FDA to conduct toxicology and other preclinical studies prior to initiation of a trial in the US. Patient recruitment for the European study was scheduled to begin in January 2003.