New cholesterol-lowering drugs show promising results in trials


There’s a new class of potentially important drugs in development that could dramatically lower LDL cholesterol levels, and the story of this class of drug begins at UT Southwestern Medical Center.

Ten years ago, researchers at UT Southwestern made the discovery that individuals who lacked the protein PCSK9 had startlingly low levels of LDL cholesterol, yet seemed to suffer no ill effects from these very low levels of “bad cholesterol.”

Pharmaceutical companies were immediately intrigued by the possibilities and began developing drugs that worked as antibodies to inhibit the function of PCSK9 protein. 

In March 2015, the first results of two clinical trials of PCSK9 inhibitors were released at the annual meeting of the American College of Cardiology, and the results were highly encouraging.

Both studies included patients with existing cardiovascular disease, some of whom had cardiovascular risk factors and some with a genetic condition that causes very high cholesterol. Both studies also included patients with high LDL cholesterol levels that were not lowered sufficiently by statins, drugs which are the current gold standard for cholesterol treatment.

The results: A dramatic 50-percent reduction in all cardiovascular events at 12 to 18 months.

Because PCSK9 inhibitors lower cholesterol to unprecedented levels, particular attention was paid to the safety of the drugs in these two trials.

As a physician who is also a scientist, I want to temper excitement about these potential new drugs with a degree of caution. Because these drugs are antibodies, they must be administered by subcutaneous injection, which means they would not be appropriate for everybody. More important, larger and longer studies of PCSK9 inhibitors are ongoing, and we must wait for the results of these more definitive studies to be confident of the effectiveness and, especially, safety of these drugs.

But for patients who cannot take statins because of complications, or for whom statins do not sufficiently lower their cholesterol level, a highly effective alternative – one which emerged from work at UT Southwestern – has appeared in the offing.