Drugs

FDA Says it Hasn’t Abandoned LDL-C Lowering as a Surrogate Endpoint

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). 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) 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.

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome