December 01, 2014
By Donna Peck
|Patrick Moriarty, M.D.|
An experimental antibody drug may be effective in lowering LDL cholesterol in patients who have difficulty tolerating traditional statin cholesterol medications. Patrick M. Moriarty, M.D., a professor of medicine and the director of clinical pharmacology at the University of Kansas Medical Center, was the lead researcher in a clinical trial on the effectiveness and safety of the drug alirocumab in lowering LDL cholesterol. Moriarty presented the results of the clinical trial at the American Heart Association's annual meeting in Chicago in November.
Alirocumab belongs to a new class of drugs that block a naturally occurring protein called PCSK9 that prevents the liver from removing LDL cholesterol from the blood.
"It was our hope that alirocumab would not only be more effective in lowering LDL, but also that patients would not experience the serious side effects seen with statin drugs," said Moriarty.
Moriarty estimated that as many as half the patients referred to his clinic have trouble taking statins such as atorvastatin (Lipitor) and simvastatin (Zocor) due to the side effects, most often muscles aches and pains. The study involved more than 360 patients from 67 sites worldwide who had LDL levels above 190, and 50 percent of the subjects had a history of cardiovascular disease. All of the study's patients had experienced statin intolerance to at least two or more drugs.
Moriarty said the study has yielded three important results so far.
"This research shows that alirocumab is effective in lowering LDL in statin intolerant patients, it is very safe in these patients and that statin-intolerant patients are a very difficult population to diagnose and, more importantly, to treat."
Patients were initially exposed to a placebo for four weeks to evaluate true statin intolerance. During this period, 13 percent of the patients dropped out with a majority complaining of muscular side effects. The remaining patients were then randomized into three double-blind treatment groups taking alirocumab, ezetimibe or atorvastatin for 24 weeks.
Moriarty says the study found that the alirocumab group experienced a 45 percent drop in their LDL levels, compared to a 14.6 percent drop in patients taking ezetmibe, another cholesterol lowering drug often used for patients who unable to tolerate statins. To further validate statin intolerance, the third group had been given the statin drug atorvastatin. When it came to analyzing side effects, 18.3 percent of the alirocumab-treated patients dropped out due to adverse events, compared to 25 percent of the patients being treated with ezetimibe and 25.4 percent of the atorvastatin patients. Even though there were significantly less muscle complaints with alirocumab, the dropout rate was not significantly different than the other groups.
After the 24 week double-blind treatment period all of the patients were placed on open-label alirocumab for two years. Interim analysis of these patients demonstrated a dropout rate of less than 3 percent.
One potential drawback to alirocumab is that unlike traditional cholesterol-reducing medications which are taken orally, it is administered by injection once every two weeks. Still, the early results on alirocumab are encouraging news for patients with statin intolerance.
Moriarty said alirocumab and another PCSKp inhibitor (evolocumab) are now being tested with two outcome trials involving 18,000 and 27,000 patients with cardiovascular disease. Regeneron, the pharmaceutical company that developed alirocumab and evolocumab, has submitted a request to the Food and Drug Administration for early approval, perhaps as soon as mid-to-late 2015.
"It is exciting to me that we may be on the verge of discovering a new class of medication that is effective and well-tolerated by the millions of people who have high cholesterol," Moriarty said.