The Food and Drug Administration has approved the PCSK9 inhibitor alirocumab as a treatment for hypercholesterolemia, making this the first drug in this class – and the first injectable, biologic lipid-lowering therapy – to be approved in the United States.

Reflecting the votes and comments of an FDA advisory panel at a June 9 meeting, the FDA approved alirocumab for a narrower indication than that proposed by the manufacturers. The approved indication is an adjunct “to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia [HeFH] or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.”

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It will be marketed as Praluent, by Sanofi-Aventis US and Regeneron Pharmaceuticals. The company said the wholesale acquisition cost is $40/day, or $14,600/year.

“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 Office of New Drugs, Center for Drug Evaluation and Research, said in the FDA statement announcing the approval. Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood. “By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels,” the FDA statement said.

In five placebo-controlled studies of people with HeFH or who were otherwise at high risk for myocardial infarction or stroke and were taking maximally tolerated doses of a statin, with or without other lipid‑modifying therapies, LDL cholesterol was reduced by 36% to 59%, compared with placebo, according to the FDA statement. In these studies, almost 2,500 individuals were treated with alirocumab. The most common adverse events associated with alirocumab included itching, swelling, pain, or bruising at the injection site, and nasopharyngitis. Hypersensitivity vasculitis (and hypersensitivity reactions requiring hospitalization have also been reported, according to the statement.

The prescribing information includes a “Limitations of Use” statement that says that the effect of alirocumab “on cardiovascular morbidity and mortality has not been determined.”

Noting that many clinical trials have shown that statins reduce the risk of MI or stroke, the FDA’s statement refers to the ongoing cardiovascular outcomes study evaluating the effects of adding alirocumab to statins on cardiovascular risk. That study – the ODYSSEY Outcomes trial – is randomizing patients with recent acute coronary syndrome who are on high-intensity statin treatment to alirocumab or placebo and is evaluating a major adverse cardiovascular event endpoint, a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.

In a statement released by the American College of Cardiology shortly after the announcement, ACC president Kim Allan Williams Sr., said that “the ACC eagerly awaits the results of the clinical trials that are in progress.” Until the CV outcomes data become available, expected in 2017, “we continue to recommend physicians limit prescribing to the very high risk, hard-to-treat groups approved by the FDA and otherwise follow the current guidelines, which recommend lifestyle change and, if needed, statins for most patients with or at risk of heart disease,” he added. In addition to being president of the ACC, Dr. Williams is chief of cardiology at Rush University Medical Center in Chicago. He has no relationships with industry.

The proposed indication for approval was for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks, and supported approval in some patient populations, such as those with HeFH; there was also some support for statin-intolerant patients and patients who cannot get to goal on statin therapy alone and are at a high cardiovascular risk, but not for others, such as those with mixed dyslipidemia.

On July 24, Regeneron and Sanofi-Aventis announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use had recommended that alirocumab be approved in Europe for treating “certain adult patients with hypercholesterolemia.”

The FDA is expected to announce the decision on evolocumab by Aug. 27. Evolocumab’s proposed indication includes patients aged 12 years and older and adults with homozygous FH (HoFH).

The prescribing information is available at http://1.usa.gov/1KpIU82.

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