The FDA has approved Lipfendra (enlicitide), the first once-daily oral PCSK9 inhibitor for adults with high cholesterol.
The medication is designed to be used alongside diet, exercise, and maximally tolerated statin therapy to further reduce LDL, or "bad," cholesterol.
Clinical trials found the pill lowered LDL cholesterol by 56% to 59% over 24 weeks, with a safety profile that was generally similar to placebo.
The U.S. Food and Drug Administration (FDA) has approved Lipfendra (enlicitide), making it the first oral medication in a class of drugs known as PCSK9 inhibitors. Until now, medicines that block the PCSK9 protein have only been available as injectable treatments.
Lipfendra is approved for adults with hypercholesterolemia, including those with an inherited form of the condition called heterozygous familial hypercholesterolemia (HeFH).
“By harnessing the innovative science of PCSK9 inhibitors and novel macrocyclic peptide technology, LIPFENDRA was designed to significantly lower LDL-C in the form of a convenient once-daily pill,” Dr. Dean Y. Li, president, Merck Research Laboratories, said in a news release.
“This is a pivotal moment as we bring the first U.S. FDA-approved oral PCSK9 inhibitor to adults with high LDL-C, offering patients an important new option. We’re proud of our work with regulators on this rigorous and efficient review process.”
The risks of high cholesterol
The medication is intended to be used along with diet and exercise to help reduce low-density lipoprotein (LDL) cholesterol, often referred to as "bad" cholesterol. It is also designed to be used in people who are already taking the highest dose of statin they can tolerate but still need additional LDL-lowering treatment.
High cholesterol often has no noticeable symptoms, which is why many people don't know they have it until a routine blood test reveals elevated LDL levels. Over time, excess LDL cholesterol can build up inside artery walls, increasing the risk of serious cardiovascular problems such as heart attack and stroke.
How the treatment was studied
The FDA's approval was based on two Phase 3 clinical trials involving a total of 3,207 adults with severe high cholesterol. Both studies were randomized, double-blind and placebo-controlled, meaning participants were randomly assigned to receive either Lipfendra or a placebo, and neither the participants nor the researchers knew which treatment each person received during the study.
All participants were already taking maximally tolerated statin therapy but still required additional cholesterol lowering. One study enrolled adults with established atherosclerotic cardiovascular disease or those considered at high risk for developing it. The second focused exclusively on adults with heterozygous familial hypercholesterolemia. Researchers measured how much participants' LDL cholesterol changed after 24 weeks of treatment compared with placebo.
The medication is taken as a once-daily tablet and works by blocking the PCSK9 protein, which helps the body remove more LDL cholesterol from the bloodstream.
What the findings mean for consumers
In the first trial, participants taking Lipfendra experienced an average 56% reduction in LDL cholesterol after 24 weeks compared with placebo. In the second trial involving people with inherited high cholesterol, LDL levels fell by an average of 59% compared with placebo.
The safety results were also encouraging. In one study, side effects occurred at similar rates in the Lipfendra and placebo groups. In the trial involving inherited high cholesterol, diarrhea and dizziness were reported more often among people taking the medication, but treatment discontinuation rates due to side effects were similar between the two groups.
For consumers, the approval introduces a new way to receive a PCSK9 inhibitor without injections. While the medication isn't intended to replace healthy lifestyle habits or statins, it provides another option for adults whose LDL cholesterol remains too high despite existing treatment, potentially making this type of cholesterol-lowering therapy more accessible for some patients.