Merck's REVEAL results could spell end to CETP class
- Merck & Co. surprised the industry when it announced in June that its cholesteryl ester transfer protein (CETP) inhibitor anacetrapib reduced major coronary events in the REVEAL outcomes study.
- Yet, full data released by the big pharma on Tuesday showed the drug only reduced the risk of major coronary events by 9% compared with placebo.
- While analysts hadn’t placed high expectations on the CETP inhibitor, Merck’s stock traded down slightly Tuesday morning after release of the data at the European Society of Cardiology 2017 Congress and simultaneously publication in The New England Journal of Medicine.
When Merck said in June the REVEAL cardiovascular outcomes study was a success (while not releasing the data), the market speculated the big pharma might have succeeded where so many of its peers had failed.
The CETP class has become a black mark on big pharmas, with the likes of Pfizer Inc., Eli Lilly & Co. and Roche all abandoning efforts in the space. Merck was the outlier when it chose to go ahead with the 30,000-patient study in 2015.
Yet, the full data from REVEAL was underwhelming at best, despite showing a statistically significant result when no other drugs in the class have. The drug had a relatively benign safety profile, only slightly increasing blood pressure and mildly reducing kidney function. But the study did show that anacetrapib stayed in the adipose fat tissues of patients for as much as five years, sparking some concerns about the drug's persistence in the body for that long.
Compared with placebo, the addition of anacetrapib to a statin regimen further reduced the mean level of non-HDL cholesterol by 18% and increased HDL cholesterol level by 104% at the study midpoint.
At a follow-up of 4.1 years, the anacetrapib group had 1,640 major coronary events, compared with 1,803 for for the placebo group — a difference of 163 events. A key secondary endpoint of the composite outcome of myocardial infarction, coronary death, or presumed ischemic stroke failed to reach significance.
"This is likely to severely curtail any potential commercial opportunity, particularly at a time when payers are even resisting paying for products demonstrating a strong CV benefit," wrote Jefferies analyst Jeffrey Holford in an Aug. 29 note to clients. "This is already reflected to a degree in consensus expectations, which only look for $223 million of sales for anacetrapib by 2021. Consequently, it would not be a surprise if Merck & Co. eventually decides not to file anacetrapib, given the likely heavy marketing expenditure that would be required to deliver only a modest return."
Merck reiterated again Tuesday morning it will continue to review the data and consult with experts before deciding whether to file for approval with the FDA and outside the U.S.
Other classes of cholesterol drugs have had trouble competing with low-cost, generic statins, which work relatively well in the majority of patients. Payers have also been resistant to covering high-priced cholesterol drugs even after they've shown a cardiovascular benefit. The market has effectively demonstrated that any new cholesterol offering would need to provide an overwhelming benefit to be commercially viable.
- Merck Press release
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