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# FDA Says it Hasn’t Abandoned LDL-C Lowering as a Surrogate Endpoint
- URL: https://www.fdaweb.com/fda-says-it-hasnt-abandoned-ldl-c-lowering-as-a-surrogate-endpoint/
- Published: 2016-06-29T12:00:00.000Z
- Updated: 2026-09-14T21:12:25.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5136089

A regulatory update by Esperion 6/28 indicated FDA may not accept low density lipoprotein cholesterol (LDL-C) lowering as a surrogate endpoint in Phase 3 studies of the hypercholesterolemia candidate, bempedoic acid ([see story](https://www.fdaweb.com/esperion-moving-ahead-with-bempedoic-acid-trials/)). Despite this uncertainty, the agency told ***FDA Webview*** 6/29 that it continues to view LDL-C as a viable surrogate in many trial settings.

“The goal of LDL-C lowering therapy is to reduce the risk for cardiovascular disease,” a CDER spokesman told us. “FDA continues to view the reduction of LDL-C as a surrogate outcome for reduced risk of cardiovascular disease. The regulatory approval of drugs such as statins was based on LDL-C, and recently, changes in LDL-C were accepted as the basis for approval of the PCSK9 inhibitors Praluent (alirocumab) and Repatha (evolocumab) in 2015\. For these recent approvals, however, FDA indicated these drugs for specific high-risk populations where, even before the availability of results from ongoing cardiovascular outcomes trials, benefit was expected to outweigh risk.”

The spokesman further noted that whenever a drug’s benefit is measured by its effect on a biomarker, such as LDL-C, “the true benefit with respect to clinical outcomes remains uncertain to some degree. A drug’s mechanism of action, magnitude of treatment effect, potential for off-target effects, and/or the target patient population could all affect the likelihood that FDA would find benefit/risk favorable to support approval of a novel LDL-C-lowering drug based on its effects on LDL-C.”

Last year, an FDA advisory committee discussed ([see meeting minutes](http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM457467.pdf?ref=fdaweb.com)) discussed the position of LDL cholesterol as a surrogate in non-statin cholesterol-lowering drugs. The committee had varying opinions. Some members stated that LDL-C remains one of the best surrogates around and that there is not much doubt that lowering LDL-C by a large amount will lead to cardiovascular risk reduction provided the drug has no off-target effects that offset this benefit. Some panel members believed that LDL-C is generally a biomarker but it can be a surrogate in some circumstances, such as when studying familial hypercholesterolemia. Others stated that whether LDL-C could be a surrogate is mechanism-dependent. And some said FDA should require outcomes data for a new drug class.