Positive results have been reported from a phase 3 trial evaluating alirocumab (Praluent, Sanofi) injection in patients with an inherited form of high cholesterol known as heterozygous familial hypercholesterolemia (HeFH), whose cholesterol levels required chronic weekly or biweekly apheresis therapy. The trial met its primary endpoint, demonstrating that patients who added alirocumab to their existing treatment regimen significantly reduced the frequency of their apheresis therapy by 75% compared with placebo (P < 0.0001). Sixty-three percent of patients treated with alirocumab no longer required apheresis compared with zero percent of placebo-treated patients.
Apheresis is a procedure whereby “bad” low-density lipoprotein (LDL) cholesterol is removed from the blood in a process similar to kidney dialysis. Apheresis therapy may be burdensome to patients, given that it can take more than three hours. Treatment can also cost up to $100,000 for each patient per year in the U.S.
The ODYSSEY ESCAPE trial involved 62 patients at 14 treatment centers in the U.S. and Germany. The patients were receiving regular baseline apheresis therapy at fixed intervals of every week or every two weeks before randomization. The patients were randomly assigned to receive 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, the 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 cholesterol response to treatment.
The most common adverse events in this study included fatigue (15% for alirocumab vs. 10% for placebo), nasopharyngitis (10% vs. 10%), diarrhea (10% vs. 0%), myalgia (10% vs. 5%), upper respiratory infection (7% vs. 19%), headache (7% vs. 5%), arthralgia (7% vs. 10%), and back pain (5% vs. 10%).
Alirocumab is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. It was approved by the FDA in July 2015 as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The effect of alirocumab on cardiovascular morbidity and mortality has not been determined.
Source: Regeneron; March 23, 2016.