FDA Approves First of Novel Cholesterol-Lowering Drugs

The U.S. Food and Drug Administration (FDA) on July 24 approved Sanofi and Regeneron Pharmaceuticals’ Praluent (alirocumab) injection, the first lipid-lowering drug in a new class of drugs known as proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. The approval comes just a little over a month after the FDA Endocrinologic and Metabolic Drugs Advisory Committee recommended two PCSK9 inhibitors for approval. The new class of drugs has the potential to offer millions of patients with high low-density lipoprotein cholesterol (LDL-C) an alternative treatment option to statins, which are associated with numerous side effects.

The FDA has approved the treatment for patients with familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease in conjunction with maximally tolerated statin therapy and diet modification. The agency notes that itching, swelling, pain or bruising at the injection site, nasopharyngitis and flu are common side effects of the PCSK9 injection treatment.

PCSK9 is a protein that controls LDL-C levels in the blood by regulating LDL receptor metabolism. Since a 2006 study first suggested that impaired PCSK9 activity might lower cardiovascular events, numerous clinical trials have been underway to study PCSK9 inhibitors. The results of two trials looking at alirocumab and Amgen’s evolocumab were presented at ACC.15. Results from the OSLER-1 AND -2 Trial showed the use of evolocumab plus standard therapy dramatically lowered LDL-C. The study found patients receiving evolocumab saw their cholesterol drop 61 percent, from a median of 120 mg per deciliter to 48 milligrams per deciliter. Reductions were sustained through the median 11-month follow-up period.

The ODYSSEY LONG TERM trial found that among patients with heterozygous FH or high cardiovascular risk, alirocumab resulted in a large reduction in LDL-C compared with placebo, which was maintained, although slightly attenuated at 78 weeks. Alirocumab appeared to be generally well-tolerated and was associated with low cardiovascular events.

While results showing the drugs' effectiveness at lowering LDL-C are promising for the new agents, definitive evidence showing the effectiveness of the drugs for reducing cardiovascular risk won’t be available until 2017 when large clinical trials are completed.

"The ACC eagerly awaits the results of the clinical trials that are in progress," said ACC President Kim Allan Williams, Sr., MD, FACC. "In the meantime, 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. Improving diet and optimizing exercise are the cornerstones of heart disease management and prevention. Statins are available as low-cost generics, are well tolerated in most patients, and their effectiveness is supported by strong evidence."

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Diet

Keywords: Anticholesteremic Agents, Atherosclerosis, Cholesterol, Cholesterol, LDL, Diet, Dyslipidemias, Disease Management, Heart Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Lipoproteins, LDL, Nasopharyngitis, Proprotein Convertases, Life Style, Receptors, LDL, Risk Factors, Subtilisins, United States Food and Drug Administration, Hypercholesterolemia


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