Since reaching the market a decade ago, PCSK9 inhibitors have not lived up to their lofty expectations. While drugs such as Amgen’s Repatha and Regeneron and Sanofi’s Praluent have proven more effective than statins at reducing “bad” cholesterol, their uptake was initially blunted by price and access limitations.
But now representing a new type of PCSK9 med is Merck’s enlicitide. The macrocyclic peptide, which was approved Thursday by the FDA and will take the commercial moniker Lipfendra, becomes the first oral PCSK9 on the market.
The FDA has endorsed a 20-mg daily dose of Lipfendra to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, a life-threatening condition in which cholesterol levels are so high that they can cause heart attacks or stroke. The nod includes patients with heterozygous familial hypercholesterolemia (HeFH).
While other PCSK9 treatments are injected, Lipfendra brings a daily oral option. The pills, which can be stored at room temperature, carry a list price of $315 per month before discounts, a Merck spokesperson told Fierce, adding that the company plans to make Lipfendra available through the direct-to-patient TrumpRx program. The list price is roughly half that of other PCSK9 products on the market, including Novartis’ new blockbuster Leqvio, which uses siRNA technology.
The downside for Lipfendra is that it can interact poorly with food, requiring an eight-hour fast before it can be taken and a 30-minute pause before food can be eaten afterward. The challenging regime raises potential questions about patient compliance.
Analyst consensus has Lipfendra reaching annual peak sales of $5 billion. Merck is anticipating Lipfendra will help compensate for the oncoming loss of patent protection for its cancer superstar Keytruda, which generated $31.7 billion, or 55% of the company’s revenue last year. With news of the approval, investors bumped Merck’s share price up by 3%.
The FDA nod was backed by two phase 3 trials, which showed that Lipfendra reduced LDL-C by 56% and 59% in patients with high cholesterol and those with HeFH, respectively, compared to placebo at 24 weeks.
While the trials showed that Lipfendra provided reductions in atherogenic lipoproteins associated with atherosclerotic cardiovascular disease (ASCVD), it is not yet known if the treatment can reduce the risk of cardiovascular morbidity and mortality, Merck said. A clinical trial is ongoing to determine this, the company added.
The FDA approved Lipfendra under the Commissioner’s National Priority Voucher (CNPV) program, which slashes review times from 6-12 months to 1–2 months for drugs that align with national health priorities. Products selected for the program generally include those that offer innovative breakthroughs, address large unmet needs or bolster domestic manufacturing.