Winter holiday time: snow, family, presents and food. Lots of food! With turkey, roast potatoes, mince pies and mulled wine all around, most people overindulge during the festive period even before dessert has been served. A study published recently in The European Journal of Clinical Nutrition found that the average weight gain over the holiday period (from Thanksgiving to New Year's Day) is around 0.8 kg, which does not seem too bad. The problem is that this additional weight is often not lost during the year, and the result can be first overweight and eventually obesity.
Obesity is linked to serious negative physical, economic and societal effects. For example, one study demonstrated that obesity can reduce the life time of a healthy nonsmoker by almost ten years. That's missing out on ten years of presents! Of course the first treatment that is recommended by every physician is lifestyle change, but if that does not work, and bariatric surgery is not an option, weight-loss drugs could be the solution. However, the number of drugs available on the market is very small, particularly in Europe.
Despite this, recently approved antiobesity agents in the United States have experienced limited uptake. This might be because the risk-benefit profile of these novel drugs has not convinced prescribers, or it may be due to caution over historical safety issues. We may learn more about the acceptance of novel antiobesity drugs this year, with the FDA and EMA expected to play a rather late Santa and approve two shiny new agents in the United States and Europe, respectively, in 2014: Orexigen Therapeutics/Takeda's Contrave (oral naltrexone/bupropion fixed-dose combination) and Novo Nordisk's liraglutide 3mg injectable preparation.
Liraglutide (Novo Nordisk's Victoza) is already approved for the treatment of type 2 diabetes, and off-label use for the treatment of obesity does occur. A study conducted in obese subjects without diabetes showed significant benefits with liraglutide 3mg (Astrup A, 2012): a placebo-adjusted mean weight loss of 5.8 kg, as well as an average of 3.8 kg more weight loss than orlistat (Roche's Xenical, generics). In the same study, liraglutide showed decreases in the two-year prevalence of prediabetes and metabolic syndrome (with each reduction of more than 50 percent). Liraglutide 3mg is efficacious, but gastrointestinal (GI) adverse events (AEs) are very common with GLP-1 receptor agonists, and associations with increased heart rate and cancer have been documented.
Contrave has shown promising results in its phase III trial program, with more than half of the recipients achieving weight loss of at least 5 percent in one trial (Apovian CM, 2013). A marketing authorization application was made to the EMA in October 2013, and a new drug application was resubmitted to the FDA in December 2013. Still, Contrave has been associated with psychiatric AEs, particularly sleep disturbances, which may make a proportion of obese patients question whether it is worth taking the drug. Additionally, negative effects on blood pressure and heart rate after one year were seen in phase III trials. However, in November 2013, Orexigen announced successful results from the interim analysis of the Light Study, which met the prespecified criteria to exclude excess risk of major adverse cardiovascular (CV) events in patients receiving Contrave as compared to placebo.
Although the weight-loss results for these emerging therapies are only modest, if approved, they will provide further assistance for patients struggling to lose weight in the New Year. We expect that Contrave's convenient oral formulation and supporting safety data will give it an edge in patient share over liraglutide 3mg, although physician familiarity and the expected high price of the liraglutide 3mg preparation are likely to see greater total sales for this drug than for Contrave.
So how good are these gifts, really. Well, neither agent may have all the bells and whistles, but the approvals of these new drugs in the United States and Europe are sure to be seen as welcome additional treatments by physicians and obese patients alike.
Business Insights Analyst Tim Blackstock, M.B. Ch.B., and Data Analyst Stefanie Matlok, M. Sc., are part of the Cardiovascular, Metabolic and Renal Disorders team at Decision Resources Group.
In-depth analysis of the obesity area, with accompanying epidemiology driven sales forecast models, is presented in Decision Resources. Obesity Pharmacor. The 2013 edition was published on October 31.