With a market worth more than US$20.1 billion, drug companies have long competed in a race to develop cholesterol medicines that work better than statins. Today, researchers report on a little-known alternative — an epigenetic therapy that fights plaque-hardened arteries in a novel manner.
Lipitor, the world’s best-selling drug as of 2011, and other statins on the market work by inhibiting an enzyme involved in the production of low-density lipoprotein (LDL) cholesterol — otherwise known as ‘bad’ cholesterol. Although the drugs help some patients with atherosclerosis who are at risk of heart attack and stroke, they fail others. And many patients respond only to high doses of statins, which predisposes them to pain, nausea, liver toxicity and other unfortunate side effects. Thus, the hunt revolves around boosting ‘good’ cholesterol, or high-density lipoprotein (HDL), in addition to halting LDL production. HDL mops up the LDL piled high in arteries and brings it to the liver for dismantling.
For a while, it seemed that the pharmaceutical giant Pfizer would be the first to put just such a medicine on the market. Their drug called torcetrapib raised HDL levels in phase II studies, but the phase III trial was terminated early when researchers realized that more patients in the treatment arm were dying of heart disease than those in the control group.
The problem might have been that torcetrapib simply put more HDL in circulation without ensuring that it acted as it should, explains Donald McCaffrey, president of Resverlogix, a small drug-development company in San Francisco, California.
Today, Resverlogix announced that in a phase II, 176-person trial, their epigenetic drug not only put more HDL in circulation but also seemed to improve the function of HDL by boosting levels of the main protein that HDL relies on to act, Apo-A1. “We think our drug will reverse the plaque build-up that causes hundreds of thousands of deaths each year,” McCaffrey says. He expects phase III trials to begin in late 2013.
Just as exciting to the drug-development world at large, Resverlogix’s compound targets an epigenetic bromodomain protein. Because bromodomain proteins have recently been linked to everything from cancer to HIV to male fertility, Resverlogix’s trial bodes well for those realms because patients in the trial have suffered no adverse reactions.