LOS ANGELES — People who can’t take cholesterol-lowering drugs called statins may someday have an alternative drug option that works about as well. Three new studies show that antibodies developed to target specific proteins in cells can knock down LDL, the so-called bad cholesterol, at a rate comparable to the highly successful statins, which go by brand names including Lipitor and Crestor.
The experimental drugs take a unique biological approach to clearing LDL from the blood, suggesting that they might replace statins in people who cannot abide those drugs’ side effects, particularly muscle pain. The new drugs may even work in conjunction with statins in people who inherit extremely high cholesterol.
Called biological products or “biologics” because they are made in living cells, the new drugs may fill a niche currently vexing doctors. “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 Veterans’ Affairs Medical Center in Atlanta. Wilson, who wasn’t part of these studies, estimates that 5 to 15 percent of people who need statins can’t take them. “We now have biologics to treat this hyper-cholesterolemia, and they’re effective.”
The new drugs, including AMG-145 and RN-316, are still in the testing stage. But researchers offered tantalizing early results November 5 at a meeting of the American Heart Association. Cardiologist Evan Stein of the Metabolic and Atherosclerosis Research Center in Cincinnati reported that people with very high LDL who got AMG-145 injections every four weeks experienced a 41 to 51 percent drop in LDL scores by 12 weeks, depending on the dose. That study was also released online in the Journal of the American Medical Association.
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Another AMG-145 study showed LDL reductions of 43 to 55 percent in people with inherited high cholesterol. Those findings also appeared 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. “This is a new drug that shows a lot of promise, but there’s still a long way to go,” he said.
The drugs are antibodies that free up a protein on cells called the LDL receptor that lowers LDL by pulling it out of circulation. The antibodies do this by targeting a troublesome protein called PCSK9 that binds to LDL receptors, bogging them down.
“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 and fight high cholesterol all their lives, he said. Statins alone often don’t get their LDL levels into the safe range.
This line of research has come full circle. 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.”