Evolocumab Lowers LDL in Statin-Intolerant Patients

January 23, 2014

THOUSAND OAKS, CA — Treating statin-intolerant patients with evolocumab (Amgen, Thousand Oaks, CA) significantly lowers LDL-cholesterol levels, according to the top-line results of the GAUSS-2 study announced today[1].

Evolocumab is an investigational human monoclonal antibody for proprotein convertase subtilisin-kexin type 9 (PCSK9). The company said the study met both co–primary end points, including the percent reduction from baseline in LDL-cholesterol levels at week 12 and the mean percent reduction from baseline in LDL-cholesterol levels at weeks 10 and 12.

The study included 307 patients who were unable to tolerate at least two different statins because of muscle-related side effects. Patients were randomized to one of four treatment groups: subcutaneous injection of evolocumab 140 mg every two weeks plus oral placebo; subcutaneous injection of evolocumab 420 mg once monthly plus oral placebo; subcutaneous placebo every two weeks plus oral ezetimibe (Zetia, Merck) 10 mg daily; or subcutaneous placebo monthly plus oral ezetimibe 10 mg daily.

The mean percent reductions observed with evolocumab were statistically significant at both doses when compared with the placebo- and ezetimibe-treated patients.

In terms of side effects, 7.8% of patients in the evolocumab arm reported headaches, as did 8.8% in the ezetimibe arm. Myalgia was observed in 7.8% of the evolocumab patients and in 17.6% of those treated with ezetimibe. Just over 6% of patients treated with the novel PCSK9 inhibitor reported pain in their extremities or muscle spasms.

Amgen recently reported positive top-line results with evolocumab in MENDEL-2 and DESCARTES . In MENDEL-2, patients had LDL-cholesterol levels ranging from 100 mg/dL to 189 mg/dL and were not receiving drug therapy. In DESCARTES, individuals with hyperlipidemia received evolocumab on top of background lipid-lowering treatment, including ezetimibe and high-dose atorvastatin.

Amgen plans to review the GAUSS-2 data and submit the results for presentation at a cardiology conference and for publication.

As reported by heartwire , monoclonal antibodies are a busy research area, with several pharmaceutical companies developing drugs. Pfizer and Sanofi/Regeneron are also working on PCSK9 inhibitors, which are in various stages of development and in general have shown LDL-lowering prowess similar to evolocumab. Sanofi and Regeneron announced today that they are collaborating with the American College of Cardiology (ACC) in a manner that will help identify eligible patients for the upcoming phase 3 ODYSSEY OUTCOMES trial with alirocumab. The ACC will identify candidates for PSCK9 treatment through its PINNACLE registry. It is the first time the registry will be used for clinical-trial recruitment.

Amgen sponsored the GAUSS-2 trial.

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