Amgen Reports Efficacy Of Evolocumab In Phase 2/3 Trials

On the heels of the Food and Drug Administration’s (FDAs) acceptance of its Biological License Application (BLA), Amgen reports new data for evolocumab in high cholesterol. Amgen announced the results from three analyses in a press release, stating that evolocumab significantly reduced lipoprotein(a) over 64 weeks and that two dosing regimens were clinically equivalent. Amgen is presenting the findings at the American Heart Association (AHA) Scientific Sessions 2014.

Investigator Frederick J. Raal, M.D., Ph.D., from the University of Witwatersrand in Johannesburg, said, "Historically, epidemiologic studies have shown a consistent and independent association between increased lipoprotein(a) and cardiovascular disease risk; however, current therapeutic options to reduce lipoprotein(a) are limited. Results from these pooled studies show that evolocumab has significant effects across the lipid profile and was effective in reducing lipoprotein(a) over a year of treatment."

Evolocumab

Evolocumab (AMG 145) is a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein hampers the liver in eliminating low-density lipoprotein cholesterol (LDL-C), the “bad” cholesterol from the blood. Elevated LDL-C levels pose a risk for cardiovascular events. The FDA recently accepted Amgen’s BLA for the agent and is expected to take action on the submission by Aug. 27, 2015. Evolocumab is currently an Orphan Drug for homozygous familial hypercholesterolemia (HoFH).

Long-Term Efficacy

Earlier trials of evolocumab have shown efficacy in the short term while the new data delivers efficacy results in the long-term. Amgen conducted three separate analyses of Phase 2 and 3 evolocumab studies. One analysis showed a significant reduction in lipoprotein(a) over 64 weeks. The efficacy in the long-term is consistent in average lipoprotein(a) reduction in the earlier (12-week) trials.

Another data set showed balanced adverse events in patients who achieved LDL-C levels of <40 mg/dL and those with >40 mg/dL levels. In an evaluation of two dosing regimens, once every two weeks or once a month, investigators found clinical equivalence, providing patients with dosing flexibility.

Amgen continues to study evolocumab in the PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations) series of clinical trials. The large and comprehensive program includes 22 trials, and Amgen hopes to enroll over 35,000 patients.