Roche’s Good Cholesterol Drug Shows Negative Side Effects

Roche Holding AG (ROG)s abandoned heart drug dalcetrapib, designed to raise levels of good cholesterol, also boosted blood pressure and inflammation, researchers said.

Dalcetrapib marks the second failure in what was expected to be a new blockbuster class of heart medicines known as CETP inhibitors. The Basel, Switzerland-based drugmaker halted development of the drug in May, saying an early look at study results found the medicine wasnt helping patients. Pfizer Inc. (PFE) dropped its pill torcetrapib in December 2006 after studies showed it raised blood pressure and boosted death rates.

The findings presented today at the American Heart Association meeting in Los Angeles showed dalcetrapib had unexpected side effects that may have contributed to its downfall. While it didnt increase hypertension in the same manner or amount as torcetrapib and there werent more deaths, its possible the medicines could have damaged blood vessels, the researchers said. That may have implications for Merck & Co. (MRK) and Eli Lilly & Co. (LLY), who are developing similar compounds.

It was a surprise that the blood pressure effect was evident, since earlier studies didnt find any increase, said Gregory Schwartz, chief of cardiology at the U.S. Department of Veterans Affairs Medical Center in Denver, in an interview. Thats why its so important to do large trials, to detect small but important safety effects.

Neither Mercks anacetrapib nor Lillys evacetrapib have shown any signs of boosting blood pressure, Schwartz said. That could change in larger trials. Both medicines also raise levels of good cholesterol much more than dalcetrapib and slash bad cholesterol that chokes the arteries. The improvement in bad cholesterol levels may propel the drugs to market, he said.

Officials at Whitehouse Station, New Jersey-based Merck and Indianapolis-based Lilly said the difference in potency makes comparisons between dalcetrapib and their compounds irrelevant. The drugs are designed to inhibit a molecule known as CETP, which results in higher levels of good HDL cholesterol that is known to ferry fatty lipids out of the arteries. Still, the amount and type of good cholesterol varies between drugs.

We havent changed our confidence in the molecule, said Yale Mitchel, associate vice president of cardiovascular research at Merck. We believe the epidemiology and other evidence support CETP as a mechanism that provides a benefit.

In the Roche study known as dal-Outcomes, dalcetrapib raised good cholesterol called HDL by 30 percent and had no effect on bad cholesterol. The trial of 15,871 patients found 8.3 percent of those getting the drug died, suffered another heart attack, stroke or were hospitalized for chest pain, compared with 8 percent of those on a placebo.

What you have here is a weak inhibitor of CETP, said Jeffrey Reismeyer, Lillys senior medical director for evacetrapib. You need more inhibition than you can get with dalcetrapib, he said. The benefit of raising good cholesterol with powerful CETP inhibitors is still an important question and one that hasnt been answered. This study doesnt reflect on our development or even Mercks.

Mercks anacetrapib raises good HDL cholesterol by 140 percent and cuts bad LDL cholesterol by 40 percent, Mitchel said. Lillys evacetrapib increases good cholesterol by about 130 percent and cuts bad cholesterol by 36 percent in studies.

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Roche’s Good Cholesterol Drug Shows Negative Side Effects