EMA updates guidance on weight-lowering agents

EMA published a draft guideline last Thursday on clinical development of products to promote weight loss in obese adults. An update to 2007 guidance, the draft says 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. The prior guideline used a loss of 10% of baseline weight as 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. EMA also reaffirmed that weight-lowering agents should be neutral to or improve measures of cardiovascular risk.

The new guidance also adds a section on methods of ruling out CV risk before submission of an MAA. A CV outcomes study is recommended when a safety concern is identified in preclinical or clinical trials, or if there is a risk associated with the molecule or mechanism of action, but the guidance does not specify the size or duration required for such a trial. EMA recommends a composite endpoint of major cardiovascular events (MACE). For compounds without CV risks identified in preclinical or clinical studies, at least 12 months of meta-analytical data and analysis of risks based on medical literature are recommended. ...