Micardis Prophylaxis Should Have Only Limited Patient Population, Cmte. Says
This article was originally published in The Pink Sheet Daily
Executive Summary
High-risk patients intolerant of ramipril need an alternative to the angiotensin-converting enzyme inhibitor, FDA's cardio-renal advisory committee concludes.
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Unmet need won the day for Boehringer Ingelheim's Micardis during a July 29 meeting of FDA's Cardiovascular and Renal Drugs Advisory Committee, which recommended that the drug be approved to reduce cardiovascular events in high-risk patients who cannot tolerate ramipril. The five-to-two vote followed the panel's unanimous rejection of the angiotensin receptor blocker's prophylactic use in the entire population of high-risk patients. The clinical trials failed to prove Micardis (telmisartan) is effective for the general high-risk population and there is a chance it would be substituted for ramipril, Ralph D'Agostino, Boston University, said in rejecting the broader indication. But there is a need to help patients who are intolerant of ramipril, and telmisartan "possibly could address it," he added. Micardis is a reasonable choice for ramipril-intolerant patients "who otherwise would be on nothing," committee Chairman Robert Harrington, Duke University, explained his vote. Sydney Wolfe of Public Citizen's Health Research Group cast one of the "no" votes, contending that a significant number of patients do not yet take the full regimen of other drugs - such as lipid-lowering medications - that are used to treat heart disease and could reduce cardiovascular risks. Most of the discussion centered on statistical analysis and the non-inferiority margin in the pivotal ONTARGET trial in which telmisartan was compared to ramipril, an angiotensin-converting enzyme inhibitor. The trial employed 1.13 as the margin; FDA statisticians favored a more conservative 1.08 (Also see "FDA, Boehringer Disagree On Non-Inferiority Margin For Micardis Prophylaxis" - Pink Sheet, 27 Jul, 2009.). The primary endpoint - a composite of myocardial infarction, stroke, cardiovascular death and hospitalizatioin for heart failure - failed to meet FDA's margin, although a three-fold composite, which dropped the hospitalization measure, did. Telmisartan currently is approved for hypertension. The specific indication sought in the sNDA under review by FDA is to reduce the risk of MI, stroke, death from CV causes or hospitalization for congestive heart failure in patients 55 years or older who have a high risk of developing major cardiovascular events. -Cathy Dombrowski ([email protected] ) |