New Diabetes Drug “Galida” Will Not File For Approval Until 2007

Galida is one of AstraZeneca’s two main drugs in final Phase III tests. Galida (tesaglitazar) is a dual-acting oral peroxisome proliferator-activated receptor (PPAR) agonist. It is a member of a new class of drugs with potential for the treatment of glucose and lipid abnormalities associated with type 2 diabetes and the metabolic syndrome.

Galida is poised to enter phase III trials having successfully completed early clinical development. Dual-acting PPAR agonists are a novel group of compounds that activate nuclear transcription factors. By activating both PPAR-alpha and PPAR-gamma receptors, they simultaneously reduce atherogenic triglycerides, raise cardioprotective HDl levels and improve insulin resistance. Thus, they address many of the core features seen in people with metabolic syndrome and may help to reverse the underlying disease process and its adverse clinical sequelae, which includes CVD and diabetes.

Drugs that target only PPAR-gamma receptors, the PPAR-gamma agonists or thiazolidinediones, are insulin-sensitisers that are already licensed for the treatment of type 2 diabetes. These agents promote fatty acid uptake and glucose metabolism so increasing sensitivity to insulin in the liver and reducing blood glucose levels. However, weight gain can occur with these agents. Because dual-acting PPAR agonists also stimulate PPAR-alpha, which influences lipid homeostasis, they address the dyslipidaemia commonly seen in patients with type 2 diabetes as well as glucose metabolism. These therapeutic benefits should also be achieved without excessive weight gain.

AstraZeneca said Galida would not be filed for regulatory approval until 2007, rather than 2006 as initially expected, because more safety tests were needed. The move follows a worldwide regulatory review of the entire drug class to which Galida belongs.

In preliminary clinical studies Galida appears to have a promising pharmacokinetic porfile and to show dose-related effects on lipids, glucose and insulin. Clinical studies also suggest it is well tolerated. Safety will be a critical issue with this new class of drugs as several promising candidates have already fallen by the wayside because of adverse toxicity profiles. Adverse effects seen with some dual-acting PPAR agonists in advanced-stage development have included oedema, raised levels of hepatic enzymes and tumours in rodents. The casualties include ragaglitazar, reglitazar and, most recently, MK-767, the development of which has been discontinued.

Drugs giant AstraZeneca last week disappointed investors by saying approval of a key diabetes drug would be delayed by safety tests. AstraZeneca said in its annual business review that it had agreed to extend clinical studies on Galida by another year, meaning it will not be able to file for approval until 2007. Extended testing of Galida, which is in the final stage of clinical trials, was triggered by a worldwide regulatory review of drugs in its class.