Metabolic Disorders

Scientists in the Metabolic Disease Biology Area are looking for novel treatments for abnormalities in metabolism and associated diseases.

Examples are:

• diabetes (disordered carbohydrate metabolism)
• dyslipidaemia (disordered fat metabolism)
• anaemia (shortage of red blood cells or low haemoglobin) and other renal diseases
• osteoporosis (loss of bone minerals).

Cardiovascular disease is often grouped with metabolic disorders because it is frequently a consequence of diabetes and dyslipidemia.

Diabetes mellitus is marked by the body’s inability to utilise glucose normally. Maturity onset (type 2) diabetes is associated with modern diets containing highly refined carbohydrates, obesity and lack of exercise. Nearly 150 million people worldwide suffer type 2 diabetes and experts predict that number will double to 300 million by 2025. Roche’s discovery and development efforts target multiple mechanisms of action, reflecting the polygenic nature of this disease.

Taspoglutide (R1583) (licensed from Ipsen) is a long-acting human glucagon-like peptide-1 (GLP-1) analogue, with potential for weekly or longer administration intervals, in phase III clinical trials.

Aleglitazar (R1439) is a dual PPAR agonist and is showing promise for the management of cardiovascular disease in high-risk patients. A decision on entering Phase III clinical trials is expected to be made in the first half of 2009.

R7201 (co-development by Roche and Chugai) and R1511 are both in Phase I clinical trials for the management of type 2 diabetes.

Reduction in levels of high-density lipoprotein cholesterol (HDLC), or “good” cholesterol, are associated with increased risk of cardiovascular disease. Dalcetrapib (R1658), licensed from Japan Tobacco and currently in phase III clinical trials, raises levels of HDLC by inhibiting cholesteryl ester transfer protein (CETP) activity.