Improving Niacin for Lipid Lowering

Before the advent of statins, the B-vitamin drug Niacin® (nicotinic acid) was a standby in attempts to raise HDL-cholesterol levels and lower triglyceride levels. A serious drawback, however, was the skin flushing produced by the drug, even with normal doses. At higher doses more severe side effects can occur, but the flushing was a problem that led many patients to drop the drug.

At the recent European Society of Cardiology meeting there was a report of a large clinical study with a new combination drug: Niacin-plus-laropiprant, given the name Cordaptive®. Over 1,500 patients with abnormal lipid levels were randomly allocated to take a placebo, Niacin, or Cordaptive. The new combination had the required lipid effects – a 19% decrease in LDL-cholesterol (the bad cholesterol), a19% increase in HDL-cholesterol (the good cholesterol), and a 22% decrease in triglycerides. Importantly, however, when compared with Niacin alone, there was a reduction in moderate flushing by 60% and extreme flushing by 50%.

Dr Nissen of the Cleveland Clinic stated that the findings were, for him, a little disappointing – he had expected laropiprant to completely block the tissue receptors that trigger flushing. Dr Nissen is well-known for his skeptical opinion of pharmaceutical company-sponsored clinical research, and he was concerned that 8 of the 10 investigators in the study were Merck employees.

Cordaptive is now being reviewed for marketing by the FDA. It will be interesting to see if Dr Nissen’s concerns are duplicated by the FDA reviewers, or if they will emerge again if-and-when the FDA’s Advisory Committee considers the combination. In the meantime, we’ll make do with statins, or Niacin-plus-flushing.

Comments

[D R Sudhakar]

There is a serious problem when men of the stature of Dr. Nissen find fault with everything.

The drug Cordaptive, in all fairness must be viewed in light of the increasing need for therapies that raise levels of HDL cholesterol as a means to control heart disease. While Pfizer put in millions into trials with torcetrapib, the failure of the drug threw CETP inhibition as an approach, into near oblivion.

Newer medications are the need of the hour and with Cordaptive, Merck has shown ingenuity in harnessing Niacin for its ability to raise HDL while curbing the ubiquitous side-effect that was the largest barrier to its usage. Laropiprant is serving its purpose of overcoming flushing and this is independent of the ‘expectations’ of Dr. Nissen and the like.

Drug discovery is a very serious business that makes or mars the fortunes of the Pharma industry, which is facing severe problems with a drying pipeline and expiry of patents. Are the men of science like Dr. Nissen, going to stand and watch, expressing unhappiness as the industry that saves lives goes down? Or will there be real men among their ranks who will seize the gauntlet and work with industry in its quest for more medicines that will continue to save lives?