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Merck claims study success with PCSK9 cholesterol pill
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An experimental cholesterol-lowering pill from Merck & Co. succeeded in a pair of late-stage studies, the company said Monday.
In one study, Merck's drug, enlicitide, was tested against a placebo in people already taking statins and who have either an inherited condition that causes high cholesterol or are at risk of atherosclerosis. The second trial evaluated enlicitide against other oral therapies, such as ezetimibe, in people on statins and with abnormally high levels of fats in the blood.
Merck didn't provide specifics, but said in both cases enlicitide met all of its study objectives and demonstrated 'statistically significant and clinically meaningful reductions' in LDL-C, or 'bad' cholesterol, without any important differences in the number of adverse events. Details will be presented at a future medical meeting. Company shares climbed 2% in early trading Monday.
A decade ago, the Food and Drug Administration approved a pair of injectable treatments that could dramatically lower cholesterol in people with heart disease. The drugs, known as PCSK9 inhibitors for the cholesterol-regulating protein they target, were hailed as medical breakthroughs and billed as multibillion-dollar sellers. Instead, their developers struggled to convince payers and physicians of their worth. Sales totals, until recently, have largely disappointed.
Merck believes it will have better luck with enlicitide, which could be the first oral medication that blocks PCSK9. The company has bet heavily on its future, enrolling about 17,000 participants across several late-stage studies. And it's counting on enlicitide to become one of the products that can help it grow sales once the patents protecting Keytruda, its dominant cancer immunotherapy, expire later this decade. Questions about its post-Keytruda future have spurred a 40% share slide over the last year and heightened pressure on its next prospects to succeed.
The company, for its part, has spoken boldly about enlicitide's promise. Research chief Dean Li has described it as likely becoming the first of its kind available, the 'most effective' cholesterol-lowering pill medicine on the market, and the foundation for future drug combinations.
Enlicitide should also be able to sidestep the reimbursement issues long weighing down sales of PCSK9 blockers, CEO Robert Davis said during a presentation in January. Though the drug is a so-called macrocyclic peptide and thus more complicated to make than traditional small molecule pills, Merck has invested significantly in production and believes it can manufacture enlicitide at a low cost. That could help the company 'price it in a way that won't create the excess challenges' others have had and obtain a 'competitive advantage,' Davis said.
Still, there is a large collection of branded and generic cholesterol drugs available, as well as multiple newer medicines in advanced testing. AstraZeneca, for one, has a PCSK9 pill in development that some analysts believe to be a meaningful threat to Merck's program. While there are 'early signs' Merck's drug might be more effective, AstraZeneca's could be 'more tolerable and easier to administer,' Leerink Partners analyst Daina Graybosch wrote in April.
The size of enlicitide's effects in Phase 3 testing, then, will be closely scrutinized. In Phase 2 trials, a variety of enlicitide doses lowered LDL levels by up to 60% after eight weeks of treatment. One of the Phase 3 studies Merck reported on Monday tested cholesterol levels after 24 weeks, and there is typically a 'degradation in efficacy' when companies move a drug into larger, longer trials, wrote Jefferies analyst Dennis Ding.
Ding also speculated that drug adherence could be lower in Merck's studies, as food intake disrupts enlicitide effectiveness. 'The magnitude of benefit will be key to watch,' he wrote.
