Porton Down, UK; November 28 2012: GW Pharmaceuticals plc (AIM:GWP) reports results from a Phase IIa exploratory study which has identified GW’s novel cannabinoid, GWP42004, as a potential new oral treatment for type 2 diabetes. In the study, which examined a number of clinically relevant endpoints in patients with type 2 diabetes, GWP42004, an oral cannabinoid treatment, showed consistent evidence of anti-diabetic effects.
Dr Garry Tan, formerly of the University of Nottingham and now Consultant Physician at NIHR Biomedical Research Centre in the Oxford Centre for Diabetes, Endocrinology & Metabolism, and the study’s Principal Investigator, said, “The positive findings from this early stage exploratory study are very encouraging. Even in small numbers of patients, GWP42004 shows consistent evidence of anti-diabetic effects. The data clearly support advancing GWP42004 into further clinical development. If larger studies confirm these findings, GWP42004 would have the potential to offer a novel orally-administered treatment option within one of the largest therapeutic areas where there still exist serious unmet medical needs.”
This 5-arm study was a 13 week randomised, double blind, placebo controlled, parallel group, pilot study of GWP42004 (5mg), GWP42003 (100mg) and two separate ratios (5mg:5mg and 100mg:5mg) of GWP42003:GWP42004. Each treatment was formulated as oral capsules and administered twice daily.
The exploratory study enrolled a total of 62 type 2 diabetes patients, such that each treatment group had 11-14 patients. Due to this small sample size per group, 10% statistical significance levels were applied (i.e. p<0.1) and identification of consistent trends were considered a key objective of the study. The study has identified GWP42004 as the company’s lead candidate in this therapeutic area and showed that it has the following desirable anti-diabetic effects:
Statistically significant results:
- Reduced fasting plasma glucose levels (p=0.04), with an increase in fasting insulin
- Improved pancreatic beta-cell function (p=0.0074).
- Increased serum adiponectin (p=0.0024) – an increase in adiponectin is considered desirable
- Reduced systolic blood pressure (p=0.099) – a desirable effect in a patient population with increased cardiovascular morbidity
- Reduced serum IL-6 levels (p=0.076) – the inflammatory cytokine IL-6 been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic β-cells, and neuroendocrine cells).
- Increased insulin sensitivity: (+4.99 change for GWP42004 vs a -4.26 change for placebo, non-significant trend p>0.1)
- Raised GLP-1 (62% increase from baseline, non-significant trend p>0.1), GLP-1 (glucagon-like peptide-1) is a natural hormone that mediates insulin secretion in a glucose dependent manner. In type 2 diabetics, GLP-1 levels are reduced leading to both poor insulin secretion and reduced pancreatic islet insulin content.
- Reduced serum C-Reactive Protein (CRP) levels (p=0.1) – Elevation of C-reactive protein (CRP) is associated with an increased risk of insulin resistance.
Several of these findings are consistent with pre-clinical data generated in collaboration with Professor Mike Cawthorne at the GW Metabolic Research Laboratory, University of Buckingham. In particular, pre-clinical data show that GWP42004 protects the insulin-producing cells of the pancreatic islets, a highly desirable feature of a new anti-diabetic medicine, increases insulin sensitivity, and reduces fasting plasma glucose levels.
Although patient numbers in the study are small, the data offer the hypothesis that the mechanism of action for GWP42004 may be that it acts as an oral GLP-1 (glucagon-like peptide-1) secretagogue. GW plans to undertake additional research to further evaluate this hypothesis. Injectable GLP-1 agonists are emerging as an important new class of treatment to treat type 2 diabetes and an oral product that stimulates GLP-1 release is likely to be attractive both to patients and to the pharmaceutical industry. The study did not show meaningful effects for GWP42003 and the other cannabinoid ratios. There was also no improvement in the pre-specified primary endpoint of HDL cholesterol, an endpoint which had been selected based on pre-clinical data for GWP42003. These study findings therefore achieve the important objective of identifying GWP42004 as the lead candidate in this therapeutic area and allowing GW to direct future GWP42004 research on anti-diabetes endpoints.
The study drugs were well-tolerated, with only 4 patients withdrawing from the study due to adverse events. Overall, a slightly greater proportion of patients experienced adverse events on placebo than on study drug (93% vs 77%).
Dr Stephen Wright, GW’s R&D Director, said, “We are very pleased that the promising results seen for GWP42004 in our pre-clinical research have been borne out in this first early proof of principle clinical trial. Key findings include the preservation of beta cell function and evidence across a number of endpoints suggesting an increase in insulin sensitivity. GW will now move ahead to explore the clinical relevance of the desirable anti-diabetic features of GWP42004 across a range of doses in a larger Phase 2 study in 2013.”