The race for the next big cholesterol-fighting drug

A battle is officially on to produce the first drug in a new class of cholesterol lowering medications.

PCSK9 inhibitors have yielded promising early stage trial results for two different products at the American College of Cardiology Scientific Session in Chicago.

PCSK9 inhibitors have been developed based on previous research that revealed blocking the PCSK9 protein, which stands for proprotein convertase subtilisin/kexin 9, prevents it from binding to LDL receptors on the liver, and impairing the liver’s ability to properly filter bad cholesterol from the blood.

LDL cholesterol - so-called "bad cholesterol" -  is a major health problem, contributing to development of heart disease, which is the leading cause of death in the U.S.

The PCSK9 inhibitors were created using genetic technology to produce a lab-created protein called a monoclonal antibody. The antibody prevents PCSK9 protein from impairing the liver’s LDL receptors.

Last week Phase one clinical trial results were published in the New England Journal of Medicine, for experimental drug REGN727, which is in development by drug makers Sanofi and Regeneron.

On Sunday, drug maker Amgen announced positive phase one results for their experimental PCSK9 inhibitor, known as AMG 145.  Among the 51 study subjects - people with high cholesterol who were taking statins - researchers found that adding AMG 145 significantly reduced LDL cholesterol levels by up to 81%. Adverse events included inflammation in the nose and throat, blood spots under the skin at the injection site, and upper respiratory tract infection. The adverse event rates were similar for placebo and AMG 145.

“Based on these results, Amgen initiated a robust Phase 2 program that will provide a deeper understanding of the benefit-risk profile of inhibiting PCSK9 in a wide variety of patients whose high cholesterol cannot be controlled with existing therapies,” said Dr. Sean E. Harper, of Amgen in a written statement, adding “We look forward to seeing the results of these studies later this year.”

Competing researchers presented Phase 2 trial results for REGN727, which are also published online in the Journal of the American College of Cardiology . The dose-finding results revealed that people who received REGN727 at two-week intervals were able to significantly reduce their cholesterol levels 40% to 72%, compared to 5% in patients who received placebo. While the trial also tested four week dosage intervals, the researchers found that the results were better sustained when the drug was given at two-week intervals.

Six patients, all receiving REGN727, stopped the therapy due to adverse events which included headache, injection site reactions, and diarrhea. One patient dropped out of the trial due to a fear of injections.

“The feeling I had when I saw the results was the feeling I had when we were studying statins in our research center,” recalls lead study author and licensed doctor of pharmacy James M. McKenney, adding “it’s important to note that these are early trial results that need to be studied in much larger populations, for longer durations.”

PCSK9 inhibitors, if they are proven safe and effective in future trials, have the potential to benefit patients who've been unable to take statin drugs due to adverse effects. They also hold promise  for patients trying to lower their cholesterol who haven't responded well to statin therapy alone.

Other monoclonal antibody drugs include treatments for rheumatoid arthritis, multiple sclerosis, and cancers.

The potentially high cost of these drugs has provoked concerns.

One CNN source estimates the cost of the REGN727 clinical trials to be in the billions of dollars - suggesting that, if the drug passes medical scrutiny, it likely would come with a high consumer price tag.

Long term side effects of the PCSK9 inhibitors will be carefully watched and studied. Other monoclonal antibody drugs have produced long-term side effects such as heart and kidney problems, and high blood pressure.

In addition to Amgen, Sanofi and Regeneron, products are being developed by Pfizer, Merck and Novartis. While experts are cautiously optimistic and excited about the potential of PCSK9 inhibitors, they'll be looking to see if more extensive studies prove that the drugs can lower heart disease rates without harming patients.