By AMERICAN HEART ASSOCIATION NEWS
For the first time in decades, the U.S. Food and Drug Administration on Friday approved a major new class of medicines to lower cholesterol, and thereby protect against heart attacks.
Praluent (alirocumab) from Sanofi and Regeneron Pharmaceuticals received approval and a second drug, Repatha (evolocumab) from Amgen Inc., is set for a decision on Aug. 27. Both injectable drugs, called PCSK9 inhibitors, received a green light early last month from an FDA advisory group.
The drugs both decrease low-density lipoprotein – the “bad” LDL cholesterol – by targeting the PCSK9 enzyme that regulates how much LDL the liver can flush from the body. Statins, the current major therapy for high cholesterol, work differently in that they block the liver’s production of LDL cholesterol in the first place. High cholesterol can contribute to plaque build-up in arteries that feed the heart and brain, which can lead to heart disease, blockages, and strokes.
Clinical trials have shown a decrease of as much as 46 percent to 64 percent, whether used by themselves or with statin drugs. The drugs would be injected ever two or four weeks and could be done at home.
Praluent was approved for use, with diet and maximized use of statins, for patients who have genetic conditions that cause high levels of LDL or who have had heart attacks and strokes and need more help lowering LDL.
The advisory panel’s recommendations in favor of the drugs and the FDA’s decision Friday come before any final results from a full clinical-outcome study, which won’t be complete until at least 2017.
But Dr. Robert H. Eckel, an endocrinologist and professor at the University of Colorado Anschutz Medical Campus and director of the medical school’s Lipid Treatment Clinic, said the drugs already are showing a positive benefit in clinical trials and could help a tough class of patients who can’t lower their dangerously high LDL on other therapies.
The FDA panels made clear the drugs should be an option for these toughest-to-treat patients.
“The risks are fairly small as we currently understand them,” said Eckel, who testified before the FDA on behalf of alirocumab. He said his appearance was not to promote that specific PCSK9-inhibitor but to give a doctor’s point of view on the need for more LDL-lowering options for specific patients. The outcome trials are being powered by large numbers, about 9,000 to 27,000 people, Eckel said.
Eckel‘s lipid clinic sees many patients who have maxed out on their current therapy with statins, who don’t tolerate statins well or who have familial hypercholesterolemia (FH), a genetic disorder that results in levels of LDL that are two-to-three times normal in approximately one in 300 people. The genetic defects make the body unable to remove LDL.
Some of these patients must then turn to a costly apheresis process similar to dialysis whereby their LDL is removed through mechanical means. Only several dozen or so places around the country offer the process.
The AHA revised its scientific guidelines about cholesterol in 2013. They de-emphasize the setting of specific LDL targets and recommend statin use for all at-risk patients with elevated LDL. The recommendations also suggest statin treatment for people who don’t have cardiovascular disease but who by using an at-risk estimator tool are determined to have at least a 7.5 percent risk of developing it over a decade.
Now with the possibility of having ultra-low levels of LDL, Eckel, who sat on that guideline-writing panel, said it is unclear whether there will be a move soon to rewrite the guideline to take into account the developments with PCSK9 inhibitors.
“Some people feel the guideline could be re-written now and others believe it should wait until the PCSK9 outcome trials are completed,” he said.
The buzz about the ultra LDL-lowering drugs has also prompted discussion about costs. Dr. William Shrank, chief scientific officer at CVS Health, estimates they will cost $7,000 to $12,000 a year.
GlobalData, a medical analytics company, predicts the two drugs, Praluent and Repatha, will eventually deliver sales about about $16.7 billion in the United States, five major markets in Europe, Japan and China by 2023.
The powerful effect of the PCSK9 gene that these drugs block was discovered by researchers at University of Texas Southwestern Medical Center.
Dr. Helen Hobbs, professor of internal medicine and molecular genetics, and colleague Dr. Jonathan Cohen, professor of genetics and development, focused on participants in the Dallas Heart Study, which Hobbs launched in 1999. They found participants born with the PCSK9 gene mutated so it did not function. They had low LDL and seemed to be protected against heart disease.