Broad smiles all round for Sanofi-Aventis yesterday after a potential star in its pipeline, Acomplia (rimonabant), was cleared for marketing by the European Commission for use alongside diet and exercise in treating overweight and obese patients who are showing signs of dyslipidaemia and other risk factors associated with the condition.
Sanofi-Aventis is targeting patients with so-called cardiometabolic risk factors - including high LDL cholesterol and hypertension - that predispose an obese patient to develop type 2 diabetes or cardiovascular problems. Of growing importance, it says, is the role of abdominal obesity - so-called the 'apple' versus 'pear' shape - which has a particular association with the emergence of insulin resistance, low levels of the 'good' HDL-cholesterol, high triglyceride levels and raised inflammatory mediators such as C-reactive protein.
A recent meeting heard from Julian Halcox, a senior lecturer in cardiology at the British Heart Foundation, about the growing recognition of abdominal obesity's role in the development of macro- and microvascular complications. “Visceral fat [that contained within the abdominal cavity] is an active endocrine organ that promotes insulin resistance, for example, by stopping the liver metabolising glucose,” he explained. Visceral fat is also linked to raised inflammatory markers such as interleukin-6 and tumour necrosis factor-alfa, as well as reduced levels of the insulin promoter adiponectin. “If you can reduce body weight by 10%, your total cholesterol level will be reduced 10%, your LDL-c by 15% and your fasting glucose by 50%. In addition, your 'good' HDL-c will be boosted 8% and - most significantly - you will lose approximately 30% of your visceral fat. The abdomen is one of the first places fat is mobilised from, which is why it causes problems in the first place,” he finished.
The approval was based on data from a 6,600-patient study dubbed RIO, which found Acomplia dramatically cut overall weight and, importantly, waist circumference. It also had a beneficial effect on HbA1c - a measure of blood glucose - triglycerides and HDL-c: in fact, the label granted by the European Commission states that an estimated 50% of the observed improvements in HbA1c, triglycerides and HDL-c were beyond that expected from weight loss alone.
A first-in-class offering, Acomplia works by selectively blocking CB1 receptors found in the brain and other organs that play an important role in glucose and fat metabolism. However, it has not been all plain sailing en route to market. Earlier this year it was forced to put back the anticipated launch date for Acomplia after being sent an approvable letter for the drug by the US Food and Drug Administration. Sanofi-Aventis had originally scheduled a launch in the first half of this year, but is still clearly hoping to win a nod during the second half.
Despite this, Acomplia is widely tipped to become a future blockbuster and represents a key player in the Sanofi's growth strategy. It is hoped that the drug will help the company to overcome generic erosion of sales of some of its key players, including the antihistamine Allegra (fexofenadine), the diabetes drug Amaryl (glimepiride), Arava (leflunomide) for arthritis and DDAVP (desmopressin). In fact, a recent report from Decision Resources revealed that the metabolic syndrome market looks set to nearly double over the next few years, leaping from $9.5 billion in 2004 to just shy of $18 billion in 2014. Analysts are predicting the market will be driven by Acomplia, with revenues in excess of $3 billion a year forecast.
Acomplia will first be launched in the UK - which has seen a 70% jump in obesity over the last decade and is following 12 years behind the USA - in July, and will be closely followed by Denmark, Ireland, Germany, Finland and Norway later during the second half of the year.