The US Food and Drug Administration (FDA) recently approved Merck’s Lipfendra (enlicitide), the first ever oral treatment for high cholesterol (hypercholesterolemia) and heterozygous familial hypercholesterolemia. Medical News Today asked the experts how it compares to statin treatments.
Lipfendra, which is an oral PCSK9 inhibitor that helps lower low-density lipoprotein (LDL) cholesterol, (or “bad cholesterol”), comes in pill form to be taken in 20mg daily doses.
Rigved Tadwalkar, MD, FACC, a consultative cardiologist, and director of the Digital Transformation Pacific Heart Institute in Santa Monica, California, said most people were familiar with statins, the cholesterol-lowering drugs taken by millions of people in the United States.
“They work by essentially ‘telling’ the liver to make less cholesterol by blocking an enzyme called HMG-CoA reductase, which is involved in cholesterol synthesis. By contrast, Lipfendra blocks a protein that causes the liver’s LDL receptors to be broken down.
“With more of those receptors available, the liver can pull more LDL cholesterol out of the bloodstream. We already know this mechanism from injectable PCSK9 treatments such as evolocumab and alirocumab. Lipfendra targets the same biological pathway, but delivers it in a once-daily pill rather than an injection.”
On whether Lipfendra was more effective at reducing LDL cholesterol than statins, he said it could be, “depending on what you are comparing”.
“In the pivotal trials, Lipfendra lowered LDL cholesterol by about 56% to 59% compared with placebo, mostly in patients who were already taking statins. High-intensity statins generally lower LDL cholesterol by at least 50%, while moderate-intensity statins typically lower it by 30 to 49%.”
Despite these encouraging results, however, Tadwalkar cautioned that Lipfendra was not tested head-to-head against a statin, so it would be misleading to simply call one better than the other.
“Statins have decades of cardiovascular outcomes data behind them. Lipfendra has shown powerful LDL lowering effects, while its own trial looking at heart attacks, strokes and other cardiovascular outcomes is still under way.”
He believed the new LDL cholesterol lowering pill might bring the most benefits “not on its own but as an additional option when a statin is not getting the LDL cholesterol low enough, or when the maximally tolerated statin dose is limited”.
Lipfendra can be taken with other cholesterol-lowering medications when needed.
In fact, the cardiologist pointed out, “that is how the drug was largely studied”.
“Most participants in the Lipfendra clinical trials were already taking moderate- or high-intensity statin therapy, sometimes along with another cholesterol medication. Lipfendra could therefore be used with a statin, ezetimibe or another treatment when a patient needs more LDL lowering. It would still be used alongside a heart-healthy diet and regular exercise, not as a substitute for them.”
He recommended not combining it with an injectable PCSK9 inhibitor, however.
“Since they target the same pathway, there is no established benefit to using them together, and patients taking another PCSK9 inhibitor were excluded from the pivotal trial.”
He noted that the most obvious target for the medication would be adults whose LDL cholesterol remained above an appropriate level despite their maximally tolerated statin.
“For some people, the maximally tolerated dose is a high-intensity statin. For others, it’s a lower dose, and for a smaller group, it may be no statin at all after a thoughtful evaluation of prior symptoms and treatment attempts.
“The conversation may be especially relevant for people who already have atherosclerotic cardiovascular disease, those at high risk of developing it, and people with a genetic form of high cholesterol called heterozygous familial hypercholesterolemia.”
Lipfendra may also be an appropriate alternative for those who would benefit from an injectable PCSK9 inhibitor but who would rather avoid this more invasive treatment, he added.
See more from MedicalBrief archives:
Cholesterol-busting pill gets go-ahead from FDA
Large UK study finds statins fail to lower cholesterol in over half of patients