Merck & Co. is betting a daily pill can work just as well as powerful cholesterol-lowering injections, revealing this week an aggressive plan to study in a series of large and expensive clinical trials an experimental drug it’s developing.
The drug, dubbed MK-0616, is what’s known as a PCSK9 inhibitor and targets a cell receptor in the liver that’s involved in regulating levels of LDL, or “bad,” cholesterol.
Two injectable PCSK9 inhibitors, Amgen’s Repatha and Regeneron’s Praluent, have been available in the U.S. for years. However, despite potent effects on cholesterol levels and modest cardio-protective benefits, they have struggled to gain ground among physicians and patients. (A third, Novartis’ Leqvio, was more recently approved.)
Merck’s plan was catalyzed by mid-stage study results it presented at a medical conference Monday and published in the Journal of the American College of Cardiology. The study tested MK-0616 at four different doses among 381 adults with high cholesterol and varying heart disease risk. Data showed that, after eight weeks of treatment, the drug lowered LDL cholesterol levels by between 40% to 60% compared to a placebo.
While the study was relatively small and conducted over a short period, the LDL reductions observed are in the ballpark of what was reported in testing for Repatha, Praluent and Leqvio, which are typically given on top of statins. MK-0616’s effects appeared greater, meanwhile, than another statin-alternative therapy marketed by Esperion Therapeutics.
Study participants given Merck’s pill didn’t experience any greater rate of side effects, nor were there any serious adverse events judged to be related to the drug.
With the positive data in hand, Merck is now preparing to embark on much broader testing, including lipid-lowering studies, a heart outcomes trial and supportive studies in different patient subgroups. The goal, Merck said, is “to establish MK-0616 as the preferred add-on to statins.”
"Our interest is to broaden and democratize PCSK9 inhibition as a tool for patients obtaining their LDL cholesterol [reduction goals],” said Eliav Barr, Merck Research Laboratories' chief medical officer, on a call with investors late Monday. “And that means not just secondary prevention, but also primary prevention in high-risk patients.”
Merck plans to run the cardiovascular outcomes trial — which, while costly, is essential to marketing a heart drug — in parallel with the lipid studies, potentially giving it answers sooner.
The trial program, coupled with Merck’s investment in a drug for pulmonary hypertension, is part of a cardiovascular drug vision that Merck sees contributing $10 billion in annual revenue by the middle of next decade. A heart failure drug approved a year ago that Merck developed with Bayer will also play a part.
Recently better known for its work in cancer, Merck expects its new heart drugs will cushion the loss of patent protections for current top-sellers Keytruda and Gardasil in the U.S. later this decade. Executives predict the oral PCSK9 could generate lofty sales due to its greater accessibility and potentially lower cost than injectable PCSK9s, which failed to live up to once similarly large sales forecasts.
“You provide the same efficacy to injectables in a way that is simple, in a way that is accessible around the world,” said Chirfi Guindo, chief marketing officer for Merck, on the call. “There are 40 million patients just in the US, Europe and Japan that are living with atherosclerosis secondary prevention.”
To have such a wide reach, the pill needs to be manufactured “at scale such that my colleagues down the line can offer it at an accessible value price point similar to other oral small molecules,” said Dean Li, president of Merck Research Laboratories, on the call.
MK-0616’s success also validates Merck’s small molecule drug discovery work, Daina Graybosch, an analyst at SVB Securities, wrote in a note Tuesday. “Their scientists were able to meet the target goals for molecule affinity and selectivity, avoid cold-chain and drug-drug interactions, and manufacture at scale” while competitors for various reasons ended their own oral PCSK9 programs. Novo Nordisk, for example, ended development of a rival oral PCSK9 late last year.
“Will you see other molecules coming through our pipeline in the coming years?,” Li said on the call. “The answer is yes.”