Evolocumab, an Injectable Drug, Lowers Cholesterol by 52%
New biologic found safe after 1 year (November 19)
An experimental heart medication from a new class of drugs—called PCSK9 inhibitors—lowered low-density lipoprotein-cholesterol (LDL-C) levels by 52% after 1 year, with no major increase in serious adverse events when compared with standard drugs, such as statins.
A clinical trial of evolocumab, developed by Amgen, marks the first data looking at 52 weeks of use for the new class of injectable biotech medications seen as a major advance in the field of cholesterol therapy in many years. These agents are most likely to be used in patients who cannot tolerate statins or those whose LDL-C levels remain high even after treatment with high-potency statins.
The drugs block a protein that prevents the liver from removing LDL-C from blood. In addition to Amgen, Pfizer and Regeneron with Sanofi are also testing PCSK9 inhibitors.
Data were presented at the American Heart Association (AHA) scientific meeting in Dallas, Texas, and the study was published online in the New England Journal of Medicine.
The 1,104-patient trial compared an injected dose of evolocumab 420 mg once monthly, in addition to standard therapy, with statins or other drugs versus standard-of-care drugs alone. After 52 weeks, patients who took evolocumab experienced a decline in LDL-C levels by 52% on top of statins. The researchers considered the result to be highly statistically significant.
Levels of other blood lipids also tended to improve. Triglycerides declined by about 9%, and high-density lipoprotein-cholesterol (HDL-C) increased by about 9%.
Serious adverse side effects occurred in 7.1% of patients receiving evolocumab and standard care compared with 6.3% for those receiving standard therapy alone. Side effects such as elevated liver enzymes were similar—1.8% for evolocumab and 1.6% in the control group. Potential kidney problems were noted in 1% receiving the study drug compared with 1.9% for the controls.
The serious side effects were not considered to be related to evolocumab. Adverse heart events, such as heart attacks, were slightly higher in the standard of care patients.
New cholesterol management guidelines released last week by the AHA and American College of Cardiology supported only medications that had demonstrated a reduction in heart risk, such as statins. This raises a question whether the FDA might be willing to approve drugs based on the lowering of LDL-C levels. An FDA official said the agency might be willing to approve the PCSK9 drugs without outcomes data if they did not show any unexpected toxicities.[Source: N Engl J Med, November 19, 2013 (online).]