Researchers theorize that the current increasing prevalence of obesity is primarily driven by the combination of sedentary lifestyles (i.e. the increasing prevalence of desk jobs over physical jobs, as well as lack of exercise during free time) and changes in diets, especially in developed countries. To date, pharmaceutical treatments have shown poor success rates. Efficacy has been lower than hoped for, with at best about 3-5% weight loss—not to be confused with percentage of excess weight loss, or %EWL, which is the clinical measure of obesity treatment success or failure.
Nevertheless, driven by the staggering potential market size, companies continue to work to develop efficacious and relatively safe pharmaceutical treatments for obesity. (See Report #S835 for specific drug candidates and products in development, on the market, or recently withdrawn market, and the current and future market status for these drugs, as well as devices for obesity management.)
Source: MedMarket Diligence, LLC
Pharmaceuticals for the treatment of obesity fall into a number of categories based on their functional approach to treating the condition. These include appetite suppression, malabsorption, satiety and combinations of these (e.g., Orexigen's Contrave). There is some debate in the clinical literature as to whether there is adequate distinction between appetite suppression and satiety to consider them functionally different drugs.
Other drugs, such as Amylin's Byetta, have been shown to reduce weight loss as a function of its role in managing type 2 diabetes.
Trials for pharmaceutical treatment of obesity are aggressive as drug makers aggressively seek to generate clinical data on drugs already developed that will illustrate safety and efficacy, an increasingly difficult hurdle to cross (some would say "moving target") based on the past rejections by the FDA.
Given the challenges of past drug candidates in gaining approval, and considering the untapped opportunity for obesity drugs, companies are actively pursuing multiple alternative angles to solving the obesity drug challenge:
- melanocortin receptor system
- cannabinoid receptor antagonists
- GLP-1 analogs
- methionine aminopeptidase 2 (MetAP2) inhibitor
In order to be judged effective the FDA holds that an obesity drug must meet at least one of two endpoints:
- At least 35% or more of patients on the drug must lose at least 5% of their body weight. This weight loss must be twice that for placebo, and the results must be statistically significant.
- There must be ≥ 5% difference in the mean weight loss between the active product and the placebo group, and again the results must be statistically significant.
The FDA also says that it will look at several secondary efficacy endpoints. These include blood pressure, pulse, lipoprotein lipids, and fasting glucose and insulin. However, the FDA does not limit itself to these, and may examine other metabolic parameters. The manufacturer might not learn what those other parameters are until the time of the review, and perhaps not until receiving a negative recommendation from the committee reviewing the drug, and reading the complete response letter (CRL).
With regard to obesity drugs, the FDA appears to take the position that the patients who would receive such drugs are basically healthy, so any weight management product must not only show decent efficacy, it must have no risk of causing lasting and/or serious harm to the patient. Some marketing managers say that it should come as no great surprise that drugs which appeared to be strong contenders for approval—such as Vivus’ Qnexa and Arena’s lorcaserin—received negative recommendations, given the uncertainty involved in trying to adhere to ‘draft’ guidelines. These managers also point out that the FDA routinely approves pharmaceuticals for the market which are known to have side effects, apparently judging that the cure is less harmful than the disease. Is there, then, a degree of bias within the FDA against the pharmaceutical treatment of obesity? If so, is this situation likely to improve? Whether or not a bias exists, we forecast that during the next five years, the FDA will approve several drugs for the treatment of obesity.
See further details of the pharmaceutical industry's development of obesity drugs at link.