Studies: Evolocumab shows promise in reducing LDL cholesterol in patients with genetic disorders that cause high cholesterol

Dr Harper

Recent data from 2 phase 3 studies showed treatment with evolocumab, a novel investigational low-density lipoprotein cholesterol (LDL-C)-lowering medication, resulted in a statistically significant reduction in LDL-C compared to placebo in patients with different types of familial hypercholesterolemia (FH).

FH is an inherited condition caused by a gene mutation which leads to high levels of LDL-C, or "bad" cholesterol, and premature cardiovascular disease.

The data from the studies were published in The Lancet.

The RUTHERFORD-2 study (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2), a phase 3 randomized, multicenter, double-blind, placebo-controlled trial, evaluated 329 patients with heterozygous FH (HeFH). The study showed that adding subcutaneous evolocumab (140 mg every 2 weeks or 420 mg monthly) to a stable dose of statin and other lipid-lowering therapies significantly reduced mean LDL-C by 59% to 66% from baseline compared to placebo at week 12 and weeks 10 and 12 (P<.001). At week 12, an LDL-C level of 70 mg/dL (1.8 mmol/L) was achieved by 68% of patients treated with evolocumab 140 mg every 2 weeks and by 63% of patients treated with evolocumab 420 mg monthly, versus 2% of patients in the placebo groups (P<.0001 each). Similar results were seen for the mean of weeks 10 and 12 (both doses P<.0001). The most common adverse events reported in the publication in evolocumab-treated patients were nasopharyngitis, headache, contusion, back pain and nausea. Results from the RUTHERFORD-2 study were initially presented at the American College of Cardiology's 63rd Annual Scientific Session (ACC.14) in March 2014.

The TESLA study (Trial Evaluating PCSK9 Antibody in Subjects with LDL Receptor Abnormalities) was a 2-part phase 2/3 trial that evaluated 49 patients with homozygous FH (HoFH), not on apheresis. The study showed that adding evolocumab 420 mg subcutaneous monthly to a stable dose of statin therapy and other lipid-lowering medications significantly reduced LDL-C by 31% (95% CI, -44, -18, P<.001) from baseline at week 12 compared to placebo. In patients with at least one defective LDL receptor mutation, evolocumab reduced LDL-C by 41% (95% CI, -53, -28, P<.0001) compared to placebo. The most common adverse events (more than 1 subject) in evolocumab-treated patients were upper respiratory tract infection, influenza, gastroenteritis and nasopharyngitis. Results from the TESLA study were initially presented at the 82nd Congress of the European Atherosclerosis Society (EAS 2014) in June 2014.

“Statin therapy has led to significant improvements in the treatment of familial hypercholesterolemia, however many patients are still not able to achieve desirable LDL cholesterol levels despite intensive treatment,” said lead investigator Frederick J. Raal, MD, University of Witwatersrand, Johannesburg, South Africa.

“Results from the RUTHERFORD-2 and TESLA studies show that evolocumab offers the potential to achieve significant further reductions in LDL cholesterol in these difficult-to-treat and high-risk populations,” Dr Raal said.

The studies’ results support the effectiveness of evolocumab as a treatment option for patients with both forms of FH, who struggle to manage their cholesterol levels, according to Sean E. Harper, MD, executive vice president of research and development at Amgen.

“These results, in combination with data from a number of other studies in our clinical trial program, formed the basis of our U.S. and EU filing submissions for evolocumab and we are working with regulatory authorities to bring this important treatment option to patients with significant unmet medical need,” Dr Harper said.