Potential Blockbuster Alirocumab (Praluent) Scores in Late-Stage Trial

PCSK9 inhibitor treats hypercholesterolemia

Positive results have been reported from a phase 3 study that evaluated alirocumab (Praluent, Regeneron/Sanofi) in patients with an inherited form of high cholesterol known as heterozygous familial hypercholesterolemia (HeFH) who required regular weekly or biweekly apheresis treatment. Adding alirocumab to existing therapy reduced low-density lipoprotein-cholesterol (LDL-C) by approximately 50% from baseline compared with a 2% increase with placebo. Alirocumab also significantly reduced the need for apheresis treatment by 75% compared with placebo (P < 0.0001)—the study’s primary endpoint.

Apheresis is a procedure similar to kidney dialysis in which “bad” cholesterol (LDL-C) is removed from the blood. It is usually reserved for high-risk patients with very high cholesterol who are unable to achieve their cholesterol-lowering goals on any other therapy.

The ODYSSEY ESCAPE trial involved 62 patients at centers in the United States and Germany. The patients were receiving regular baseline apheresis therapy at fixed intervals of every week or every two weeks before randomization. The average LDL-C level at baseline was 4.7 mmol/L (181 mg/dL). Ninety percent of patients in the alirocumab group and 86% of those in the placebo group had a history of coronary heart disease. The patients were randomly assigned to receive either subcutaneous alirocumab 150 mg (n = 41) or placebo (n = 21) every two weeks in addition to their existing treatment regimens. The double-blind treatment period consisted of two intervals: for the first six weeks, patients remained on their established apheresis schedule at baseline, and for the following 12 weeks, the frequency of apheresis was adjusted based on the patient’s LDL-C response to treatment.

Despite being treated with apheresis and entering the ODYSSEY ESCAPE trial with very high LDL-C levels, 63% of the patients receiving alirocumab no longer required apheresis after six weeks of therapy. At that time point, the average LDL-C level in the alirocumab-treated group was 2.3 mmol/L (90 mg/dL) compared with 4.8 mmol/L (185 mg/dL) in the placebo group.

Other key results from the ODYSSEY ESCAPE trial include:

  • Ninety-three percent of patients treated with alirocumab experienced at least a 50% reduction in their apheresis procedures (P < 0.0001).
  • Throughout the trial, patients treated with alirocumab experienced significant reductions in their LDL-C levels starting at week 6 (a 55% greater reduction compared with placebo), and lasting until the trial ended at week 18 (a 46% greater reduction compared with placebo) (P < 0.0001). 

A similar proportion of patients experienced adverse events in the alirocumab and placebo groups (76% for both groups). The most common adverse events included fatigue (15% for alirocumab vs. 10% placebo), nasopharyngitis (10% vs. 10%), diarrhea (10% vs. 0%), myalgia (10% vs. 5%), upper respiratory tract infection (7% vs. 19%), headache (7% vs. 5%), arthralgia (7% vs. 10%), and back pain (5% vs. 10%).

Source: Regeneron; August 29, 2016.