MSD gets first FDA okay for oral PCSK9 cholesterol drug

 MSD has won the race to bring an oral PCSK9 inhibitor through to regulatory approval in the US, after getting the go-ahead from the FDA for Lipfendra as an LDL cholesterol-lowering treatment.

The US regulator has cleared Lipfendra (enlicitide) as a once-daily treatment for adults with high cholesterol (hypercholesterolaemia), including those with a genetic form known as heterozygous familial hypercholesterolemia (HeFH), alongside diet and exercise.

MSD – known as Merck & Co in the US and Canada – has claimed FDA approval for the oral drug ahead of rival developers, including nearest rival AstraZeneca, whose AZD0780 is in phase 3 testing.

Currently available PCSK9-targeting therapies are Amgen's Repatha (evolocumab) and Sanofi/Regeneron's Praluent (alirocumab), both antibodies dosed monthly, and Novartis' small interfering RNA therapy Leqvio (inclisiran), which can be given twice a year.

Analysts have said that oral therapies could transform hypercholesterolaemia treatment and address a market worth billions of dollars a year in the US alone, given that many patients struggle to reach LDL cholesterol targets despite the availability of current oral therapies like statins and then injectable PCSK9 options.

Lipfendra's approval is based on the results of the CORALreef Lipids and CORALreef HeFH trials, which respectively revealed 56% and 59% reductions in LDL cholesterol at 24 weeks in hypercholesterolaemia and HeFH patients compared to placebo.

"This is a pivotal moment," said Dr Dean Li, president of Merck Research Laboratories, in a statement. "By harnessing the innovative science of PCSK9 inhibitors and novel macrocyclic peptide technology, Lipfendra was designed to significantly lower LDL cholesterol in the form of a convenient once-daily pill."

MSD is also running a large-scale cardiovascular outcomes study, CORALreef Outcomes, along with other phase 3 studies looking at long-term treatment of hypercholesterolaemia over three years, use of the drug in paediatric HeFH, and as a combination therapy with rosuvastatin.

Lipfendra is one of a series of new products that MSD is relying on to help it cope with the loss of patent protection for $31 billion cancer blockbuster Keytruda (pembrolizumab), which will start to happen around 2028.

It is also expected to be a key factor in the company's bid to expand its annual revenues above $70 billion by the mid-2030s, along with other new products like rare tumour therapy Welireg (belzutifan) and pulmonary arterial hypertension (PAH therapy Winrevair (sotatercept).

MSD told Reuters that Lipfendra will launch with a list price of $10.50 per day, based on a 30-day supply.

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