What Is Lipfendra? Understanding the New Drug Approved to Lower LDL Cholesterol

The US Food and Drug Administration (FDA) has now approved Lipfendra (enlicitide) to be used alongside diet and exercise to lower LDL-C in adults with high cholesterol and in people with heterozygous familial hypercholesterolaemia (HeFH), an inherited form of high cholesterol. Lipfendra is a once-daily oral tablet and is notable as the first oral medication to block PCSK9, a target previously addressed primarily through injectable therapies. Existing treatment options for high cholesterol include statins, ezetimibe and PCSK9 inhibitors, but this approval introduces a new oral option for eligible patients.

DISCLAIMER: This article is based on information from the public domain and/or the experts we spoke to. Always consult your health practitioner before starting any routine.

The approval is based on two randomised, double-blind, placebo-controlled clinical trials involving 3,207 adults with severe hypercholesterolaemia, including people with and without HeFH, who were already receiving maximally tolerated statin therapy. In participants with established or high-risk atherosclerotic cardiovascular disease (ASCVD), Lipfendra reduced LDL-C by an average of 56% from baseline at 24 weeks compared with placebo. In adults with HeFH, the average reduction was 59%. The safety profile was broadly similar to placebo in one trial, while diarrhoea and dizziness were the most commonly reported side effects, occurring more frequently in people with HeFH who received Lipfendra. These findings raise important questions about where this new medication fits into cholesterol management and which patients may benefit most. We asked an expert to explain.

How Lipfendra lowers LDL cholesterol

Dr Rahul Mehrotra, Chief, NIC & Clinical Cardiology, Artemis Hospitals, tells indianexpress.com, “Lipfendra (enlicitide) is the first once-daily oral drug to inhibit PCSK9, a protein that reduces the liver’s ability to clear LDL or bad cholesterol from the blood. The liver clears more LDL cholesterol by blocking PCSK9.”

He adds that Lipfendra is an oral tablet, not an injectable PCSK9 inhibitor. Dr Jagadish Hiremath, Public Health Intellectual, mentions, “Statins primarily reduce cholesterol production in the liver, while ezetimibe reduces cholesterol absorption from the intestine. Enlicitide works through a different biological pathway and can complement these therapies. Patients who continue to have elevated LDL cholesterol despite maximally tolerated statin therapy, those with familial hypercholesterolemia, or individuals who are unable or unwilling to take injectable medications may benefit the most from this treatment.”

What the trial results mean 

“A 56%-59% average reduction in LDL cholesterol is very significant as lowering LDL is directly related to lowering cardiovascular risk,” notes Dr Mehrotra, adding that these reductions can help slow plaque buildup in arteries, which over time can reduce the risk of heart attack, stroke and other cardiovascular complications. Although those trials did not examine clinical outcomes and were primarily designed to lower cholesterol, prior work has demonstrated that the greater and more persistent reduction in LDL is associated with fewer cardiovascular events, especially in people with high cardiovascular risk.

While the cholesterol-lowering effect is very encouraging, Dr Hiremath says, long-term outcome studies will ultimately determine the extent to which these reductions translate into fewer cardiovascular events. “However, based on existing evidence from other LDL-lowering therapies, substantial reductions of this magnitude are generally expected to provide meaningful cardiovascular protection over time.”

DISCLAIMER: This article is based on information from the public domain and/or the experts we spoke to. Always consult your health practitioner before starting any routine.