MSD (Merck & Co) has won US Food and Drug Administration (FDA) approval for its cholesterol-lowering pill, marking a significant milestone in the drugmaker’s push to reduce revenue reliance on Keytruda (pembrolizumab).
The FDA has approved MSD’s Lipfendra (enlicitide) to reduce low-density lipoprotein cholesterol (LDL-C) in adults with high cholesterol or who have an inherited type of high cholesterol called heterozygous familial hypercholesterolemia (HeFH). Lipfendra, which is to be used in tandem with diet and exercise, is a tablet taken once a day.
The marketing authorisation means MSD has beaten AstraZeneca to market the first PCSK9 inhibitor in pill form. AstraZeneca is hoping to unlock this indication with laroprovstat, which is still in Phase III trials.
LDL-C, also known as “bad” cholesterol, causes plaque to build up in vessels, increasing the risk of heart attacks and strokes. While lifestyle habits can cause high levels, genetics can also play a role, such as the inherited disorder HeFH. About 86 million US adults age 20 or older have total cholesterol levels above the recommended level, according to the US Centers for Disease Control and Prevention (CDC).
In one study (NCT05952856) in MSD’s Phase III programme, Lipfendra reduced LDL-C by 56% compared to placebo, and this rose to 60% when accounting for negligible baseline levels. In another trial (NCT05952869), it cut LDL-C by 59% compared to placebo. The drug also led to further benefits associated with atherosclerotic cardiovascular disease (ASCVD) risk, and its safety profile was similar to placebo, though diarrhoea and dizziness occurred at higher rates in one of the studies.
There are many options to treat high cholesterol, including statins, ezetimibe, and PCSK9 inhibitors. The latter class, which until now were only available in injectable form, works by enabling the liver to recycle more receptors that sweep LDL-C from the blood. Amgen's Repatha (evolocumab) and Regeneron/Sanofi's Praluent (alirocumab) dominate this landscape.
Katherine Wilemon, CEO of the non-profit Family Heart Foundation, commented: “We are encouraged by the approval of a new oral PCSK9 inhibitor option for adults who need additional LDL-C lowering.”
MSD sharpens post-Keytruda strategy
Lipfendra’s presence as the only oral PCSK9 inhibitor on the market represents a significant growth opportunity for MSD. Executives at the company have previously touted the commercial opportunity, though they have not yet placed a sales forecast on the medicine. GlobalData forecasts $3.5bn in global sales for Lipfendra in 2032.
GlobalData is the parent company of Pharmaceutical Technology.
MSD is contending with the impending loss of exclusivity for its flagship product Keytruda. For three years, the pan-solid tumour drug was the world’s top-selling medication, generating peak sales of $31.7bn in 2025. It has since been usurped by Eli Lilly’s weight loss drug Mounjaro (tirzepatide).
Keytruda’s core US patent expires in late 2028, with other regions following thereafter, forcing the big pharma company to diversify its portfolio to plug the looming revenue hole. It is doing this through a mixture of in-house R&D and business development. The latter strategy saw MSD strike agreements to buy respiratory disease drug developer Verona Pharma for $10bn in July 2025 and antiviral specialist Cidara Therapeutics for $9.2bn in November 2025, amongst others.
Citi analysts said in a research note: “We see Lipfendra as an important addition to MSD’s broader effort to diversify growth drivers and build greater exposure in cardiometabolic disease as Keytruda loss of exclusivity approaches”.
Dutch-based biotech NewAsmterdam’s cholesterol-lowering therapy obicetrapib, which targets the Cholesteryl Ester Transfer Protein (CETP), has been linked to a decrease in a key biomarker of Alzheimer’s disease. This suggests that drugs that clear cholesterol could have benefits in other diseases.
