FDA OKs First of New Class of Cholesterol Drugs

Praluent for people with prior history of heart attack or stroke who've already tried a statin

Friday, July 24, 2015

FRIDAY, July 24, 2015 (HealthDay News) -- The U.S. Food and Drug Administration on Friday approved Praluent, the first of a powerful new class of injected, cholesterol-lowering drugs that experts believe could change cardiovascular care.

Praluent (alirocumab) sharply cuts levels of LDL ("bad") cholesterol, and is one of a group of newly developed drugs called PCSK9 inhibitors, the FDA explained in a news release.

The drug is only approved for patients with heart disease and a history of heart attack or stroke "who require additional lowering of LDL cholesterol" in addition to taking a statin drug and adopting a healthy diet, the agency said.

It is also for use by patients with a condition called heterozygous familial hypercholesterolemia (HeFH), an inherited illness that causes people to have high levels of LDL in the blood.

"Praluent provides another treatment option for patients with HeFH or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough on statins," Dr. John Jenkins, director of the FDA's Office of New Drugs, Center for Drug Evaluation and Research, said in the news release.

Praluent may only be the first of two PCSK9 inhibitors to eventually hit the market: Earlier this month, an FDA panel also endorsed another such drug, called evolocumab (Repatha) for use in patients who are at very high risk for high cholesterol. According to the Associated Press, a decision on Repatha is due by Aug. 27.

Studies seem to back up the effectiveness of PCSK9 inhibitors in lowering artery-clogging cholesterol. One recent review of 24 clinical trials -- published in the Annals of Internal Medicine -- found that PCSK9 inhibitors lowered people's LDL cholesterol by about 47 percent, on average.

More important, the drugs seemed to cut the risk of heart attack or death from heart disease, according to the researchers.

Experts did urge some caution, however: The trials so far have been short-term, and it's not clear whether the new cholesterol drugs really do extend people's lives, according to Dr. Seth Martin, a cardiologist at Johns Hopkins University in Baltimore.

"Still, the early data are exciting, and we're cautiously optimistic," Martin, who co-wrote an editorial published with the study, told HealthDay.

However, until large clinical trials are completed in 2017, experts won't have definitive proof of whether the new drugs actually reduce the risk of heart attacks and death.

Statins have long been the go-to treatment for lowering LDL cholesterol. Studies have proven they can help prevent heart attacks, strokes and other cardiovascular complications.

But for some people, statins cause intolerable muscle pain. "Those people would be obvious candidates for PCSK9 inhibitors," Martin said.

For others, statins just don't do the job -- including people with inherited conditions like HeFH, which causes very high LDL levels and heart attacks at an early age.

"Familial hypercholesterolemia is not rare," Martin noted. "It affects about one in 300 to 500 people."

Of the trials covered in the Annals review, half involved people with familial hypercholesterolemia. Some of the others focused on people who'd dropped statins because of side effects.

PCSK9 inhibitors work by blocking a protein in the liver that helps regulate LDL cholesterol, according to the study. The new drugs don't seem to cause the muscle problems that statins can.

However, that doesn't mean they're completely safe. Martin said the main concern that has arisen in trials of the new drugs is the potential for "neurocognitive effects." For example, some study patients have reported problems such as confusion and trouble paying attention. But, Martin said, it's not clear yet whether the PCSK9 inhibitors are actually the cause.

And in the FDA news release, the agency said that side effects associated with Praluent include "itching, swelling, pain, or bruising where injection is given, [colds] and flu," as well as allergic reactions at the injection site.

For the Annals review, researchers led by Dr. Eliano Navarese, of Heinrich Heine University in Dusseldorf, Germany, pooled the results of 24 clinical trials involving more than 10,000 patients. Some compared a PCSK9 inhibitor to a placebo (inactive treatment), while others used the cholesterol drug ezetimibe (Zetia) for comparison.

Overall, the researchers found, the new drugs cut LDL to a greater degree. They also lowered patients' risk of heart attack or death by about half.

The caveat, Martin stressed, is that the studies were short, and few people suffered complications. He said longer-term studies are needed to prove that the drugs prevent heart attacks and extend people's lives -- without serious side effects.

Dr. Suzanne Steinbaum, a preventive cardiologist at Lenox Hill Hospital in New York City, agreed that the results so far are encouraging.

"For all those patients unable to take statins, finally there might be an option that can change (their) outcomes," said Steinbaum, who was not involved in the recent review.

But, she added, "we need to patiently wait for the next phase of trials to see whether the clinical outcomes are as promising as the initial studies suggest."

And drugs like Praluent are not without their downsides, experts said.

For one, the drugs have to be self-injected, which might put some people off. On the other hand, Martin said, the injections are done only once a month or every couple of weeks.

"Some people may prefer that to taking a pill every day," he said.

And then there's the cost. PCSK9 inhibitors are specialty drugs known as monoclonal antibodies, which are lab-altered versions of human antibodies. And they are not cheap.

The cholesterol drugs could cost up to $12,000 a year per patient, according to a recent estimate by CVS Health, one of nation's largest pharmacy benefit managers.

Since so many Americans take cholesterol drugs -- for years or even decades -- CVS warned that the cost to the health care system could be sky-high.

SOURCES: Seth Martin, M.D., clinical and research fellow, Johns Hopkins Heart and Vascular Institute, Baltimore; Suzanne Steinbaum, D.O., preventive cardiologist, Lenox Hill Hospital, New York City; April 28, 2015, Annals of Internal Medicine; Associated Press; U.S. Food and Drug Administration, news release, July 24, 2015

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