A federal advisory committee this week will decide whether to recommend approval of the first in a new class of drugs many experts believe could significantly cut the risk of strokes and heart attacks, a leading cause of death for Americans.
The highly-anticipated new drugs have been shown in clinical trials to sharply reduce levels of bad, or LDL cholesterol, representing the first major advance in the area since widely used statin drugs hit the market in the late 1980s.
"This is one of the biggest developments in a long time in cardiology," said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, who is involved in clinical trials for two of the new treatments under development. "The effects of these drugs are very robust."
Millions of Americans each year currently take statin drugs intended to lower levels of bad cholesterol, which can greatly increase the risk of heart disease. According to the Centers for Disease Control and Prevention, more than 73 million Americans — nearly a third of all U.S. adults — suffer from high LDL cholesterol.
But even as mainstay statins such as Lipitor have become ubiquitous in medicine cabinets across the country, there are some patients who can't tolerate the drugs, and many still can't get their bad cholesterol levels low enough. That's where the new class of cholesterol-busting drugs being considered by the Food and Drug Administration comes in.
They are known as PCSK9 inhibitors, because they block a substance that hinders the liver's ability to remove cholesterol from the blood. Unlike statins, which come in pill form, the new inhibitors are self-injected every two weeks.
Studies published this spring in the New England Journal of Medicine showed that two PCSK9 drugs currently under development — one by Amgen and another by Sanofi and Regeneron Pharmaceuticals — reduced bad cholesterol by roughly 60 percent. In many cases, the reductions occurred even in patients already taking statins.
Despite such striking results, FDA advisers considering the merits of the two drugs this week won't have a definitive answer to a key question: Even if PCSK9 inhibitors dramatically reduce bad cholesterol levels, will that actually translate into lower numbers of strokes, heart attacks and other cardiovascular problems?
Current research seems to suggest that's the case, but fuller answers won't come until the completion of longer term, larger studies over the next several years.
“I’m not sure we know the long-term effects of the drugs," said Julie Clary, a cardiologist at the Indiana University School of Medicine, who has analyzed clinical trial results. Still, she said, "The existing studies that we have certainly show promise."
Even as it waits for more conclusive results, the FDA might well decide to approve the two drugs this summer — Pfizer has a third PCSK9 inhibitor under development — based on their apparent ability to lower bad cholesterol.
"I think that's a prudent decision," said Nissen, who noted that the drugs had shown few harmful side effects thus far. "The FDA appropriately recognizes that the unmet need for lowering cholesterol is sufficiently large."
The potential costs of the new drugs is causing consternation among some health-care providers and insurers. While the companies involved have not yet said what they might charge, some experts have estimated that the drugs might cost $10,000 a year. That pales in comparison to specialty treatments for conditions such as cancer and hepatitis C. But it is far more than the cost of statins, many of which are now available in cheap generics, and the overall burden could skyrocket given the sheer number of patients who might eventually take PCSK9 inhibitors.
Nissen noted that while the potentially high prices for the new cholesterol-fighting drugs are worrisome, the alternatives are neither cheap nor preferable. "Bypass surgery and coronary stenting is pretty expensive," he said. "Heart attacks are not a pleasant thing."
Katherine Wilemon of California suffered her heart attack at 39. She has familial hypercholesterolemia, an inherited disorder that can severely elevate LDL levels. According to a 2014 study in the journal Circulation, an estimated 1 in 299 Americans has the disease.
Her episode came during a time when her doctor had taken her off statins while she was trying to become pregnant. Back then, her disease remained undiagnosed. It took years before a specialist figured out Wilemon’s problem and she was able to enroll in a clinical trial for a PCSK9 inhibitor, in addition to statins and other therapies. Her LDL now is in the high 40s, considered a target range for people who have previously suffered heart attacks.
Wilemon started the FH Foundation to spread the word about the disease and increase screening to find people who have it.
“Without the new drug, my total cholesterol was about 200. The consistent message was that put me at severe risk” for more cardiovascular problems because of the previous heart attack, said Wilemon, now a mother of two young girls, one of whom also has the inherited disorder. “The bottom line is it’s very exciting for heart disease [treatment] in general, but absolutely essential for a population like ours.”