EMA Updates CV Safety Analysis of New Heart, Metabolic Drugs 

Sponsors of new drugs to treat cardiovascular and metabolic diseases should use a composite of all major cardiovascular events as the primary endpoint in studies to establish CV risk, the European Medicines Agency says.

In some cases, additional CV outcomes like hospitalization for other cardiovascular causes could be included in a composite endpoint. The use of a MACE-plus endpoint — defined as a composite endpoint comprised of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for unstable angina — should be justified based on being more sensitive to detect any harmful CV effects of the drug candidate, the EMA says.

The agency recommends two approaches for assessing CV risk: a meta-analysis of data from Phase 2 and 3 studies or a dedicated CV outcome study. An outcome study should have a control arm and, in the case of an active control, the CV risks should be well-established, according to a reflection paper.

Size and duration of trials will depend on the number of events being observed. Sponsors should strive for a study population similar to the target population, with a sufficient number of high-risk patients.

Drugmakers should include a summary of results from the CV safety analysis in the summary of product characteristics in the marketing application.

The reflection paper is meant to be used in conjunction with existing guidelines on clinical investigation of new drugs.
Comments are due Sept. 30. View the reflection paper at www.fdanews.com/06-15-15-CVrisk.pdf. — Meg Bryant