Arena issued with obesity patent

Arena's APD356 is currently undergoing Phase 2 clinical trials, which are studying the molecule's efficacy on the 5-HT2C serotonin receptor. The G protein-coupled receptors are located in the part of the brain called the hypothalamus. APD356 has approximately 100-fold selectivity in vitro for the 5-HT2C receptor relative to the 5-HT2B receptor. Arena believes this receptor is primarily implicated in the cardiac valvulopathy observed with non-selective serotonergic drugs.

During previous trials, APD356 was discovered to have approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the 5-HT2A receptor, the central nervous system (CNS) receptor thought to be responsible for most of the CNS adverse effects of non-selective serotonergic agents.

Arena​ believes the selectivity of APD356 for the 5-HT2C receptor may allow the compound to be dosed at a well-tolerated level that will induce clinically relevant weight loss without the side effects observed with non-selective serotonergic agents.

Obesity and a related condition known as metabolic syndrome affect tens of millions of adults and children in the US and pose a serious long-term threat to their health and welfare. In the last 10 years there has been a 30 per cent increase in the incidence of obesity in the USA and that about 30 per cent of the population of the USA is now considered obese.

Approximately two-thirds of all adults in the US are obese or overweight and 16 per cent of children and adolescents ages 6 to 19 in the US are overweight. Medical and related costs of obesity in the US were more than $117 billion (€91 billion) in 2000. Being obese or overweight is associated with a number of conditions, including heart disease, stroke, diabetes, cancer and osteoarthritis.

Most currently marketed products have been unsuccessful as treatments for obesity due to a lack of efficacy or unacceptable side-effect profiles. The most successful drug so far has been the indirectly acting 5-hydroxytryptamine (5-HT) agonist fenfluramine (Redux) but reports of cardiac valve defects in up to one third of patients led to its withdrawal by the FDA in 1998.

In addition, two drugs have recently been launched in the USA and Europe: Orlistat (Xenical), a drug that prevents absorption of fat by the inhibition of pancreatic lipase, and Sibutramine (Reductil), a 5-HT/noradrenaline re-uptake inhibitor. However, side effects associated with these products may limit their long-term utility. Treatment with Xenical is reported to induce gastrointestinal distress in some patients, while Sibutramine has been associated with raised blood pressure in some patients.

The patent (publication number - BR0309303) is entitled: "5-HT2C Receptor Modulators," and was issued by the European Patent Office.