PCSK9 Inhibitor Achieves Positive Results in Phase 3 Trial

Praluent lowers LDL cholesterol in patients with heterozygous familial hypercholesterolemia (HeFH).

A phase 3 trial of the cholesterol-lowering PCSK9 inhibitor alirocumab (Praluent) injection achieved positive results in patients with heterozygous familial hypercholesterolemia (HeFH) who were receiving LDL apheresis treatment.

Praluent is designed to lower LDL cholesterol levels in the blood. It is the only PCSK9 inhibitor available in 2 dosages, with 2 levels of efficacy (75-mg and 150-mg). These results were reported from the phase 3, double-blind, placebo-controlled ODYSSEY ESCAPE trial.

There were 62 patients from 14 treatment centers in the United States and Germany enrolled in the study. Prior to randomization in the study, participants underwent apheresis therapy at fixed intervals on a weekly or bi-weekly basis.

Apheresis is an invasive and expensive procedure that is typically reserved for high-risk patients with very high cholesterol and who are unable to achieve their cholesterol-lowering goals on any other therapy. Apheresis is similar to kidney dialysis, where LDL cholesterol is removed from the blood.

The average LDL cholesterol at baseline was 4.7 mmol/L (181 mg/dL), with 86% of participants in the placebo group and 90% in the Praluent group having a history of coronary heart disease.

The participants were randomized to receive 150-mg Praluent (n=41) subcutaneously every 2 weeks or placebo (n=21), in addition to their already existing apheresis treatment regimen. For the first 6 weeks of the trial, patients stayed on their established apheresis treatment schedule at baseline.

The following 12 weeks, the frequency of the apheresis therapy was adjusted based on the patient’s LDL cholesterol response to treatment. The results of the study showed that after 6 weeks of treatment with Praluent, 63% of patients no longer required apheresis therapy.

During this same time point, the average LDL cholesterol level among the Praluent group was 2.3 mmol/L (90 mg/dL), compared with 4.8 mmol/L (185 mg/dL) in the placebo group. The recommended LDL cholesterol target levels from European guidelines is between 1.8-3.0 mmol/L (70-115 mg/dL) depending on the risk of cardiovascular disease.

“Findings from ODYSSEY ESCAPE suggest a role for Praluent in the overall management of patients with HeFH undergoing regular apheresis therapy, with the potential to reduce the need for burdensome apheresis treatments,” said Patrick M. Moriarty, MD, professor of the Department of Internal Medicine; director of Atherosclerosis and Lipoprotein Apheresis Center, University of Kansas Medical Center. “This is a significant development in the continued investigation of this drug in HeFH patients, because it is the first clinical trial to demonstrate that Praluent reduced the frequency of apheresis therapy.”

Key findings from the study included: 93% of patients in the Praluent group experienced at least a 50% reduction in their apheresis procedures; throughout the trial, the Praluent group experienced significant reductions in their LDL cholesterol starting at week 6, which was a 55% greater reduction compared with placebo, and lasted to the end of trial (45% greater reduction compared to placebo).

In both groups, there were a similar amount of patients who experienced adverse events (AEs). The most common AEs were fatigue, nasopharyngitis, diarrhea, myalgia, upper respiratory infection, headache, arthralgia, and back pain.

ODYSSEY ESCAPE is part of the overarching phase 3 ODYSSEY program, which includes more than 25,000 patients, and the results were presented at a Hot Line session at the ESC Congress 2016 in Rome, Italy.