PCSK9 inhibitor is safe and effective in phase 2 randomized trial

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Patients with primary hypercholesterolemia who received subcutaneous injections of LY3015014 had a significant decrease in low-density lipoprotein (LDL) cholesterol, according to a phase 2, randomized, double-blind, placebo-controlled study.

They also tolerated the medication, which was taken along with other lipid-lowering therapies, including statins. In addition, there were durable reductions of non-high-density lipoprotein cholesterol, apolipoprotein B and lipoprotein A.

LY3015014 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor that is not yet FDA-approved.

Lead researcher John J.P. Kastelein, MD, of the University of Amsterdam in the Netherlands, and colleagues  published their results online in the  European Heart Journal on Jan. 12. Eli Lilly and Co., the manufacturer of LY3015014, funded the study.

Between June 2013 and January 2014, they enrolled 527 patients at 61 community and academic centers in North America, Europe and Japan. Patients received 20, 120 or 300 mg of LY3015014 every four weeks; 100 or 300 mg of LY3015014 every eight weeks; or placebo.

All patients were between 18 and 80 years old and had primary hypercholesterolemia, which was defined as LDL cholesterol of 80 mg/dL or higher and trigyclerides of 450 mg/dL or below.

Patients were required to be on a stable diet and were allowed to use ezetimibe or statins for at least six weeks.

The researchers examined patients every two weeks during the 16-week treatment phase and at follow-up visits at four and eight weeks following completion of treatment. At each visit, they obtained LDL cholesterol and safety laboratory measurements.

The mean age of patients was 58.4 years old, while 53.6 percent were male and 68.6 percent were white. In addition, 10.0 percent of patients received 40 or 80 mg of atorvastatin or 20 mg to 40 mg of rosuvastatin, 69.7 percent took another statin or dosage and 20.2 percent did not use a statin. Further, 13.9 percent received ezetimibe.

Patients who received LY3015014 during the study had a mean LDL cholesterol reduction of between 14.9 percent and 50.5 percent, while the placebo group had a mean increase in LDL cholesterol of 7.6 percent.

The mean maximal decrease was 37.1 percent with 300 mg of LY3015014 every eight weeks and 50.5 percent with 300 mg of the medication every four weeks.

The researchers said the short-term safety profile of LY3015014 was similar to other PCSK9 inhibitors. They added there were no treatment-related serious adverse events and no liver or muscle safety issues. The most common adverse events associated with  LY3015014 were injection site pain and injection site erythema.

In 2015, the FDA approved the first two PCSK9 inhibitors:  alirocumab (Praluent) and  evolocumab (Repatha). Both drugs are intended to lower LDL cholesterol.