Favorable Results With Evolocumab Announced

Over approximately 1 year, evolocumab reduces cholesterol levels by 61% and reduces cardiovascular event rates by 53% in patients with hyperlipidemia when used in conjunction with standard therapies.

In a study by Robert P. Sabatine, MD, MPH and colleagues published in the New England Journal of Medicine on March 16, 2015, investigators reported favorable results with evolocumab.

The study combined data from a total of 12 previous phase II and III trials, which were together known as the Open-Label Study of Long-Term Evaluation against LDL Cholesterol, or OSLER. A total of 4465 patients were randomized in a 2:1 ratio to receive either evolocumab with standard therapy or standard therapy without evolocumab.

Treatment lasted a median of 11.1 months, after which point investigators assessed rates of a combined end point of death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, or heart failure.

Evolocumab treatment reduced low-density lipoprotein (LDL) cholesterol from a median of 120 mg/dL to 48 mg/dL—a 61% statistically significant reduction (P <.001). Cardiovascular event rates were significantly reduced by 53%, from 2.18% to 0.95% (P = .003).

Evolocumab did more than reduce LDL levels. Levels of apolipoprotein B were reduced 47.3%, levels of triglycerides were reduced by 12.6%, and high-density lipoprotein (HDL) was raised by 7% (P <.001, all comparisons).

Serious adverse events were of identical incidence in patients receiving evolocumab and patients receiving placebo (7.5% in both groups). The rate of all adverse events, however, was slightly higher in patients receiving evolocumab (69.2%) versus patients receiving standard therapy (64.8%).

A potentially important difference in adverse event rates include a 0.9% rate of neurocognitive adverse events with evolocumab treatment versus a 0.3% rate with standard therapy. However, the rate of neurocognitive adverse events was not related to the amount of LDL reduction experienced during the trial.

Injection-site adverse events occurred in 4.3% of patients taking evolocumab, which was either injected subcutaneously once monthly at a dose of 420 mg or injected once every 2 weeks at a dose of 140 mg. A total of 6 patients discontinued treatment due to injection-site adverse events.

In a press release, Sabatine stated, “The reduction in LDL was profound and that may be why we saw a marked reduction in cardiovascular events so quickly. It suggests that if we can drive a patient’s LDL cholesterol down a large amount to a very low level, we may start to see a benefit sooner than would be expected with a more modest intervention.”

The OSLER study is an important medical advance for patients at risk for heart disease and eligible for statin therapy based on current guidelines. Evolocumab, which has a prescription drug user fee act (PDUFA) date of August 27, 2015, may be another option for the 72 million Americans who currently qualify for statin therapy.

References

• Sabatine MS, Giugliano RP, Wiviott SD, for the Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med. 2015.
• OSLER -1 and -2: PCSK9-Inhibitor Evolocumab Shown to Dramatically Lower LDL [press release]. American College of Cardiology website. https://www.acc.org/latest-in-cardiology/articles/2015/03/11/12/59/8am-pt-315-osler-1-and-2-effect-of-pcsk9-inhibitor-evolocumab-on-cv-outcomes?w_nav=LC. Accessed March 2015.
• Amgen. FDA Accepts Amge n's Biologics License Application For LDL Cholesterol-Lowering Medication Evolocumab [press release]. http://www.amgen.com/media/media_pr_detail.jsp?releaseID=1987861. Accessed March 2015.
• Shah RV, Rubenfire M, Brook RD, Lima JA, Nallamothu B, Murthy VL. Heterogeneity in statin indications within the 2013 american college of cardiology/american heart association guidelines. Am J Cardiol.2015;115(1):27-33.