Merck advances one of cardiology's holy grails

In the two decades since scientists discovered a curious genetic mutation that protects people from bad cholesterol, researchers have tried and failed to develop a pill that might replicate those effects for people at risk of heart attacks. Merck, a storied company making a return to cardiovascular medicine, believes it has succeeded where others have failed.

As STAT's Matthew Herper reports, an oral treatment from Merck lowered LDL cholesterol by 60% at the highest dose in a mid-stage clinical trial. The drug, which targets a bodily protein called PCSK9, appears to work as well as injectable medicines that have proved to prevent heart attacks and strokes but have not gained much traction. If Merck can replicate those effects in larger studies, its PCSK9 pill could become a go-to medicine.

"I believe that there's like 40,000 McDonald's restaurants in 100 countries," said Dean Li, Merck's head of research and development. "I want the PCSK9 mechanism to be available in every one of those countries. And the way you do it is you make a small molecule that can do what the monoclonal antibody can do."

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Regulatory

Califf wants to rethink those high-stakes FDA meetings

Before most new drugs make it to the market, they go through a public hearing in which a bunch of expert advisers to the FDA debate their relative merits and, usually, vote yes or no on whether they ought to be approved. To Commissioner Robert Califf, the outsized attention on just how those votes stack up is becoming a distraction.

In an interview with STAT yesterday, Califf said the real value of those advisory committee meetings is the substance of the feedback — whether from physicians, scientists, or patients — not the results of a hurried straw poll conducted after hours of discussion.

"I would like to get rid of voting as much as possible," Califf said. "That's a habit. It's not a requirement, and it's not very useful. I'd like more advisory committees to be about the thinking about the field and the intervention that's being assessed, not so much the approval decision."

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Sequencing

The genomics arms race keeps heating up

Bay Area genomics firm Pacific Biosciences will start shipping units of its new DNA sequencer on Wednesday, the company announced today, marking the latest example of the push to read DNA quickly, accurately, and affordably. The instrument, dubbed Revio, reads DNA in long chunks, an approach that can help researchers decipher more complex regions of the genome, including areas researchers missed during the original Human Genome Project.

The company says that it plans to ship 25 sequencers this quarter and that it had received 76 orders by the end of last year. PacBio's announcement adds to intense competition by companies to rival Illumina, which dominates about 80% of the current sequencing market.

These two companies have a complicated history. In 2018, Illumina announced that it planned to acquire PacBio for $1.2 billion. But the deal fell apart after the Federal Trade Commission opposed Illumina's plans, calling the company a "monopolist."

Markets

When good data go over poorly

Matthew Herper/STAT

The biggest news over the weekend at the American College of Cardiology Conference was that a cholesterol-lowering pill from Esperion met its goals of preventing heart attacks and strokes. Then yesterday came around, and the company's share price fell by 20%.

Part of that is numerical: Esperion's pill reduced the risk of cardiovascular complications by 13% relative to placebo, which is below the 15% threshold investors were looking for. The rest has to do with perception. Marketing a cardiovascular drug is an expensive proposition, and Esperion has only about $160 million in cash and a market capitalization of less than $500 million. The bull case for the company was not that it would upend pharmaceutical history by marketing its way to blockbuster sales but rather that a larger firm would swoop in to buy it for $1 billion or more.

The data, at least according to Wall Street, make that buyout look less likely. And in the meantime, Esperion is left to its own devices in the costly process of selling the drug. Hence the race car.