Long-Term Results of Evolocumab to Treat Hypercholesterolemia

Dallas—After a year of treatment, patients with hypercholesterolemia who received evolocumab plus the standard of care had a mean reduction of 50% in low-density lipoprotein (LDL) cholesterol compared with a group that took optimal standard of care alone, according to a multinational, randomized, controlled, open-label extension trial.

Evolocumab had a similar reduction on other lipid parameters such as apolipoprotein B, lipoprotein(a), and triglycerides, and the adverse effects were similar between the groups.

Michael Koren, MD, lead author of the study, presented the results at the AHA Scientific Sessions during a clinical science special report session. The findings were also published online in Circulation [doi: 10.1161/circulationaha.113.007012]. It is the largest and longest study of an anti-PCSK9 antibody reported to date, according to Dr. Koren.

Evolocumab, previously referred to as AMG 145, is a monoclonal antibody that inhibits the PCSK9 protein and is intended to treat hypercholesterolemia. In 4 randomized, placebo-controlled phase 2 studies, more than 1300 patients with hypercholesterolemia who received evolocumab had a reduction in LDL cholesterol of up to 65% after 12 weeks of treatment.

To assess the drug’s long-term safety and efficacy, patients who completed the previous studies could enter the OSLER (Open-Label Study of Long-Term Evaluation Against LDL-C) trial that took place at 155 study sites in 17 countries. They were then randomized in a 2:1 ratio to receive the standard of care plus 420 mg of evolocumab injected subcutaneously every 4 weeks (n=736) or standard of care alone (n=368).

The first 12 weeks of the OSLER study were a blinded stabilization period during which background therapy could not be adjusted. After 12 weeks, the lipid results were unblended, and investigators could change the background therapy if necessary. Patients in the evolocumab were seen at study centers every 4 weeks, while patients in the standard of care alone group were seen at week 4 and then every 3 months with interim telephone visits, according to Dr. Koren.

Following the first year of treatment, patients were allowed to take evolocumab until the study ended, which is expected to be 5 years.

The groups were well balanced. At baseline, the mean age was approximately 56 years, 88% of patients were white and 56% were female. The mean LDL cholesterol at baseline of the phase 2 trials was approximately 140 mg/dL.

Patients assigned to placebo during the phase 2 studies who were then randomized to receive standard of care during the OSLER trial had a 2% mean reduction in LDL cholesterol after 52 weeks even though they could have standard of care background medicines up-titrated following 12 weeks. Patients assigned to placebo during the phase 2 studies who were then randomized to receive evolocumab during the OSLER trial had a 52% mean reduction in LDL cholesterol after 52 weeks.

Patients assigned to evolocumab during the phase 2 study who were then randomized to continue taking evolocumab during the OSLER trial also had a 52% mean reduction in LDL cholesterol after 52 weeks. Patients assigned to evolocumab during the phase 2 study who were then randomized to receive standard of care alone during the OSLER trial had a 3% mean reduction in LDL cholesterol after 52 weeks.

At week 52, 86% of patients taking evolocumab had LDL cholesterol <100 mg/dL and 63% had LDL cholesterol <70 mg/dL compared with 16% and 1%, respectively, of patients in the standard of care alone group. In addition, 72% of patients taking evolocumab had LDL cholesterol <100 mg/dL at every visit and 38% had LDL cholesterol <70 mg/dL at every visit compared with 3% and 0%, respectively, of patients in the standard of care alone group.

Serious adverse events were found in 7.1% of patients in the evolocumab plus standard of care group and 6.3% of patients in the standard of care alone group. Dr. Koren noted that patients taking evolocumab had more visits, which could increase the reporting rate of adverse events. He added that 5.2% of patients taking evolocumab had an injection site reaction, although 1 patient stopped taking evolocumab because of an injection site reaction.