The excitement around PCSK9 — a promising protein target for cholesterol-lowering therapies — seems to be justified. This week, at the American College of Cardiology’s annual meeting in Washington DC, several pharmaceutical companies presented data from advanced clinical trials showing that monoclonal antibodies that target and degrade PCSK9 are effective at treating patients with high cholesterol, especially when combined with statins such as Lipitor.
PCSK9, which circulates in the blood, prevents the liver from importing and processing low-density lipoprotein (LDL), or ‘bad’ cholesterol. People with genetic mutations that lower levels of PCSK9 in the blood also have lower cholesterol levels. (A 2013 feature story in Nature details how PCSK9 was discovered through the Human Genome Project.)
In one of five advanced-stage clinical trials it presented this week, Amgen, based in Thousand Oaks, California, showed that its new drug, evolocumab, lowered cholesterol by 57%, on average, in 901 patients who took the drug for a year. The company is in the process of enrolling more than 30,000 people in further clinical trials.
Evolocumab has two close competitors. One is alirocumab, made by Sanofi, based in Bridgewater, New Jersey, and Regeneron, based in Tarrytown, New York. Alirocumab lowered cholesterol by nearly 50% compared to a placebo, and by 75% when combined with a statin. Finally, New York City-based Pfizer showed that its drug bococizumab lowers cholesterol by up to 67% when combined with a statin.
Jay Edelberg, who heads PCSK9 development at Sanofi, says that monoclonal antibody treatments could be especially useful for people who cannot take statin drugs or who have a genetic predisposition to high cholesterol.
All four companies now have larger trials underway, in which they will continue testing for adverse effects and determine whether the lowered cholesterol actually decreases a patient’s risk of heart disease. If all goes well, Amgen plans to file for regulatory approval for evolocumab later this year, and Sanofi and Regeneron plan to file in 2015.