Statin substitutes show promise: injected antibody-based drugs reduce cholesterol in trials.
People who can't take cholesterol-lowering drugs called statins may someday have an alternative that works about as well. Three new studies show that lab-produced antibodies that target specific proteins in cells can knock down LDL, the "bad" cholesterol, at a rate comparable to the highly successful statins.
The experimental drugs take a novel biological approach to clearing LDL from the blood, suggesting that they might replace statins (SN: 5/5/12, p. 30) in people who cannot abide those drugs' side effects, particularly muscle pain. The new drugs may even work in conjunction with statins for people who inherit extremely high cholesterol.
"We have been bumping up against statin intolerance in patients," often in people who have had a heart attack, said Peter Wilson, an endocrinologist at Emory University and the Atlanta Veterans Affairs Medical Center. Wilson, who wasn't part of these studies, estimates that 5 to 15 percent of people who need statins can't take them.
The new drugs, including AMG-145 and RN-316, are still in testing. But researchers offered early results November 5. Cardiologist Evan Stein of the Metabolic and Atherosclerosis Research Center in Cincinnati reported that people with veryhigh LDL who got AMG-145 injections every four weeks experienced a 41 to 51 percent drop in LDL by 12 weeks, depending on dose. That study was also released online November 5 in the Journal of the American Medical Association.
Another AMG-14S study showed LDL reductions of 43 to 55 percent in people with inherited high cholesterol. Those findings also appear online in Circulation. The drug is made by Amgen.
RN-316, made by Pfizer, knocked down LDL by up to 75 percent in a 12 -week trial, reported Barry Gumbiner, an endocrinologist at Pfizer in San Diego.
The drugs are antibodies that free up a protein on cells called the LDL receptor, which lowers LDL by pulling it out of circulation. The antibodies do this by targeting a troublesome protein called PCSK9 that binds to LDL receptors.
"Cholesterol is essential for the normal functioning of cells," said Frederick Raal, an endocrinologist at the University of the Witwatersrand in Johannesburg who presented the Circulation study. Even as LDL receptors remove LDL from the blood, the PCSK9 protein acts as a brake on that process, he said. Targeting PCSK9 allows the receptors to snag more LDL.
Besides helping people who cannot take statins, Raal said, the drugs may be added to therapy in those who can tolerate statins but who fail to benefit fully from those drugs even at high doses. That includes people with hereditary high cholesterol.
Only a few hundred people in the United States have an extreme form of this condition inherited from both parents, Wilson said. But about 500,000 have inherited the condition from one parent. Statins alone often don't get LDL levels into the safe range for those people.
PCSK9 was originally found because people who lack it have few heart problems, Gumbiner said. "Their LDL levels are much lower, and they live long, healthy lives," he said. "That was the genesis for looking at this as a drug target."