On 31 July 2014, the European Medicines Agency (“EMA“) issued draft guidelines on the clinical evaluation of new medicinal products used to promote weight loss in obese adults (the “Draft Guidelines“) and has opened a public consultation on the Draft Guidelines until 31 January 2015.
The Draft Guidelines are an update of the CPMP Guideline on medicinal products used in weight control (CPMP/EWP/281/96) that was adopted by the CHMP in 2007 (the “2007 Guidelines“). The Draft Guidelines state that a reduction of body weight should be the primary efficacy endpoint in clinical studies for weight control products. A valid primary endpoint is the proportion of patients with a weight loss that is at least 5-10% of baseline weight and is also at least 5% greater than that associated with placebo. This has changed from the 2007 Guidelines, whereby weight loss of 10% of baseline weight was the threshold.
The proportion of patients with at least 5% weight loss and the impact on the risk of developing diabetes should be secondary endpoints. Comorbidities secondary to obesity, such as sleep apnoea, joint pain and depression should be assessed for the beneficial effects of the study drug.
The Draft Guidelines contain a new section on ruling out an increase in cardiovascular risk prior to submitting a marketing authorisation application. Weight loss medicines should show a neutral or beneficial effect on parameters associated with cardiovascular risk. Any claim of a reduction of cardiovascular morbidity should be supported by clinical trials that enrol a representative sample of patients with obesity. At the time of submitting a marketing authorisation application, the exclusion of an increase in cardiovascular risk of the study drug may be demonstrated by:
- at least 12 months of meta-analytical data, an analysis of medical literature and the absence of an increase in pre-clinical trials; or
- conducting a dedicated cardiovascular outcome study. The study population should mimic the target population and include a representative proportion of high-risk patients. The EMA recommends a composite endpoint of major cardiovascular events (MACE).