Here it is. phase 1 results. Regards, DH
Adherex Releases Initial Exherin Clinical Data at ASCO: Preliminary Safety Profile Satisfactory with Hints of Biological Activity
6/7/04
NEW ORLEANS, Jun 7, 2004 (BUSINESS WIRE) --
Adherex Technologies Inc. (TSX: AHX), a biopharmaceutical company with a broad portfolio of products under development, today released initial results from the Phase I study of its anti-cancer drug, Exherin(TM), at a major international cancer conference.
Exherin(TM) is a small peptide molecule that specifically disrupts the blood vessels of cancers through inhibition of the adhesion protein N-cadherin. The safety, toxicity, pharmacology and maximum tolerated dose of Exherin(TM) were evaluated in 31 treatment cycles in 20 patients with N-cadherin positive or negative tumors. Dynamic MRI was also performed where feasible to evaluate changes in tumor perfusion and intra-tumoral hemorrhage. Results demonstrated that Exherin(TM) was well tolerated in cancer patients in all five tested doses (ranging from 50 to 281 mg/m2) and no toxicity limiting further dose escalation related to the drug was identified, meaning further dose escalation can be evaluated in future studies. Some patients noted a bad taste shortly after drug administration but it required no treatment and soon dissipated. Pharmacokinetic studies showed that the blood levels of the drug in patients were predictable, linear and dose related across all tested doses.
Phase I studies are the first step in drug development following animal-based research. These studies are typically conducted on a small number of subjects and aim to evaluate a drug's safety and toxicity. In some instances, Phase I studies also provide preliminary evidence of drug efficacy.
Although not the primary focus of the study, Exherin(TM) demonstrated hints of biological activity in two patients. Commenting on the findings presented at the American Society for Clinical Oncology (ASCO) conference in New Orleans, Dr. Derek Jonker, the Principal Investigator on the study and Assistant Professor at the Ottawa Regional Cancer Centre, said: 'In this type of Phase I study, and particularly at these relatively low single doses which were well tolerated, the recognition of some biological activity will certainly encourage further study.'In one case, a 24-year-old woman experienced a drop in tumor associated cortisol levels one week after Exherin(TM) administration, with subsequent evidence of tumor necrosis on MRI scans by day 43. In a second case, a 56-year-old man showed decreases of 39% and 14% in tumor masses on MRI scans following drug administration.
'The initial findings from our study lend support to the view that targeting cadherins may be a useful approach in cancer therapy,' said Dr. William P. Peters, Chairman and CEO of Adherex. 'However, this data is only the first step in a long and uncertain process of developing this drug. Thus far, the drug is well behaved pharmacologically and well tolerated in patients and it is certainly exciting to see early hints of activity. However, research and development of drugs is inherently uncertain and unexpected toxicity or inadequate effectiveness might appear with further study. Adherex and its investigators will need to continue to systematically evaluate all aspects of this drug and related compounds to determine the safest and most effective way to use these novel agents.'
Exherin(TM) is an angiolytic compound that selectively targets tumor blood vessels. Structurally, it is a five amino acid cyclic peptide that is soluble and administered intravenously to patients. It acts by preventing N-cadherin molecules on adjacent blood vessels from binding to each other. Since this binding is essential for maintaining a blood vessel's structural integrity, interfering with it via use of an N-cadherin antagonist such as Exherin(TM) ultimately results in rupture of the blood vessel. As tumor blood vessels are structurally abnormal and have diminished adhesive properties, they appear particularly susceptible to N-cadherin antagonists. Preclinical data support this theory, and in a range of in vivo tumor models, Adherex's N-cadherin antagonists have demonstrated a highly selective tumor angiolytic activity within 60 minutes of a single intravenous drug infusion.