Details from four trials in the alirocumab ODYSSEY clinical program – ODYSSEY LONG TERM, ODYSSEY COMBO II and ODYSSEY FH I and FH II – were presented Aug. 31 during a Hot Line session at ESC Congress 2014. Alirocumab is a PCSK9 inhibitor that has shown promise in lowering LDL-C in patients with severe hypercholesterolemia who are at high risk for cardiovascular disease.

In ODYSSEY LONG TERM, study investigators compared the long-term safety and efficacy of alirocumab versus placebo in combination with maximally tolerated lipid-lowering therapy, including statins, in patients with hypercholesterolemia and at high cardiovascular risk. Overall results found that alirocumab "demonstrated safety generally comparable with maximally tolerated statin therapy with/without other lipid-lowering therapy and produced significant reductions in LDL-C." Investigators noted a majority of alirocumab-treated patients reached prespecified LDL-C treatment levels at Week 24. The 2,341-patient trial is the largest double-blind phase 3 study of a PCSK9 inhibitor with the longest follow-up, to date.

The 720-patient, double-blind ODYSSEY COMBO II trial evaluated the long-term safety and efficacy of alirocumab vs. ezetimibe in combination with a maximally tolerated statin dose. Results showed LDL-C decreased from baseline maintained with alirocumab, with a significantly greater decrease vs. ezetimibe at week 24 (51 percent vs. 21 percent (P<0.0001)). In addition, 77 percent of alirocumab patients achieved LDL-C <1.81 mmol/L (70 mg/dL) at week 24. According to Christopher Cannon, MD, FACC, self-administered alirocumab had good compliance and was well-tolerated. He noted that this "treat-to-target" approach with alirocumab resulted in ~80 percent of patients not requiring a dose increase to 150 mg at week 12.

Both the ODYSSEY FH I and FH II trials involved a total of 738 patients with heterozygous familial hypercholesterolemia (HeFH) and compared alirocumab to placebo in combination with maximally tolerated lipid-lowering therapy, including statins. Results showed that self-administered alirocumab produced significantly greater reductions in LDL-C vs. placebo at week 24, with the majority of patients (>70 percent) achieving their LDL-C goals. Approximately 50 percent of patients did not require a dose increase to 150 mg at week 24. In general, safety and tolerability were comparable in both the alirocumab and placebo groups, investigators noted.

"The cardiovascular community eagerly awaits larger clinical trials which examine clinical endpoints with this class of agents," said Kim Eagle, MD, MACC, Editor-in-Chief of CardioSource.org, professor of medicine, Albion Walter Hewlett, and director, Frankel Cardiovascular Center at University of Michigan Health System in Ann Arbor, MI.

Keywords: Follow-Up Studies, Azetidines, Hyperlipoproteinemia Type II, Cardiovascular Diseases, Risk Factors, Hypercholesterolemia