Merck: Jury Still out on ‘Good’ Cholesterol

Tuesday, 29 Jan 2013 12:45 PM


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The jury is still out on the benefits of increasing "good" HDL cholesterol, but the strategy remains worth pursuing, despite recent setbacks, the chief executive of Merck says.

Confidence in the HDL thesis suffered a fresh blow last month when a major clinical trial of Merck's Tredaptive medicine failed. That followed earlier failures with two other HDL-boosting drugs from Pfizer and Roche.

The Pfizer and Roche drugs worked differently to Tredaptive, by inhibiting a protein called CETP, and Merck is also developing a key experimental product in this area.

Merck CEO Ken Frazier, speaking in Davos on the sidelines of the World Economic Forum this month, said the U.S. drugmaker would continue to press ahead with clinical research on HDL raising, even though the scientific case so far remained inconclusive.

"The Tredaptive failure is another piece of evidence on the side of the scale that says HDL raising hasn't yet been proven," he said.

"I don't think by any means, though, that the question of HDL raising as a positive factor in cardiovascular health has been settled."

Tredaptive, which is now being taken off the market in those countries where it was sold, combined an extended release form of niacin, to raise HDL, with a drug to cut the incidence of facial flushing that is a side effect of niacin therapy.

Merck is developing another drug called anacetrapib, which targets CETP and raises HDL cholesterol by much more than niacin, to see if it can reduce risks of heart attacks and stroke.

If that trial succeeds, anacetrapib would address a huge market, and the medicine could be a decisive factor in Merck's commercial success in the years ahead.

But investors' confidence in the whole approach of lifting HDL is shaky.

"It's certainly not a slam dunk, but I believe that given the properties of the drug, it is an experiment well worth conducting," Frazier said of the ongoing anacetrapib trial.

Anacetrapib belongs to the same cholesterol-ester transfer protein (CETP) class as Pfizer's high-profile drug torcetrapib, which was ditched in 2006 due to adverse side effects, and Roche's dalcetrapib, which was dropped last year due to lack of efficacy.

On both those fronts, Frazier believes the Merck product has an edge, since there is no evidence that it causes the unwanted side effects seen with torcetrapib, and it is also able to lower "bad" LDL, which Roche's product did not.

Another similar drug, evacetrapib, is under development from Eli Lilly.

© 2014 Thomson/Reuters. All rights reserved.

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