Merck's Liptruzet may mend IMPROVE-IT, but offers little in the short run

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The approval of Merck's new cholesterol lowering combo drug Liptruzet (Zetia-plus-atorvastatin) has been met with raised eyebrows.

Newly approved Liptruzet boasts market-leading efficacy. In studies, it lowered cholesterol by 50%—making it the most effective LDL-lowering therapy available.

Bernstein Research's Tim Anderson, said of Liptruzet: “This is certainly not a ‘high-science' product, yet there is something to be said for that a drug that can boast the best LDL cholesterol lowering of any single oral agent currently available.”

So, what's the problem then? While effective, there is still no proof that Liptruzet lowers cardiovascular risk, prevents heart attacks and strokes or improves health outcomes better than generic Lipitor alone.

This has left some scratching their heads at FDA's decision: Steve Nissen, chairman of cardiology at the Cleveland Clinic, said, the approval “just doesn't make any sense,” Forbes reported.

“I find it astonishing that after all the controversy about ezetimibe [Zetia], the FDA would approve another combination product with a drug that been on the market for a decade and has not been shown to improve cardiovascular outcomes,” Nissen explained.

With another Zetia combo available besides Vytorin, Nissen also suggests that this may expose Zetia as doing little to prevent heart problems—now that it's even more widely used.

With that, Liptruzet appears destined to be a third string therapy. Physicians will be more apt to choose high doses of simvastatin, atorvastatin and Crestor—for patients who can tolerate it—since those drugs have demonstrated that they improve health outcomes and prevent cardiovascular risks in trials. Sales estimates, back when Liptruzet was expected to be approved in 2014, were expected to peak at a half billion in 2016.

It's not all doom and gloom for Merck, though. The approval of a Zetia+Lipitor combo does dial back concerns that the IMPROVE-IT Trial could show that Vytorin, or its Zetia component, is potentially harmful.

It's unlikely FDA would have approved a Zetia combo if it was concerned about IMPROVE-IT's safety record, according to Anderson: “FDA is likely privy to the general findings from IMPROVE-IT's various interim looks that have occurred, and being a risk averse agency, if there were hints of harm it would likely steer clear of approved any new Zetia formulations until full IMPROVE-IT results are in.”

Added to the green light from an independent safety monitoring board this past March to continue trials through September 2014, the FDA's action suggests an improved outlook on IMPROVE-IT.

“If this logic is right,” wrote Anderson, “then the MRK story has just been partially de-risked (at least on this one event).”

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