ODYSSEY Studies Explore Safety and Efficacy of Alirocumab in High CV Risk Patients

Alirocumab produced significantly greater LDL-C reduction than ezetimibe in patients with statin intolerance, according to results from the ODYSSEY ALTERNATIVE Trial presented on Nov. 17 as part of AHA 2014.

The study randomized 314 patients to either alirocumab (75 mg self-administered injection every two weeks), ezetimibe (10 mg/day) or atorvastatin (20 mg/day) arms for 24 weeks. The alirocumab dose was increased to 150 mg at week 12 depending on cardiovascular risk and week 8 LDL-C levels.

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Overall, data showed significant differences between alirocumab and ezetimibe in the reduction of LDL-C from baseline to week 24 (-45.0 percent vs. -14.6 percent, respectively). In addition, study investigators noted that alirocumab allowed more patients to achieve an LDL-C goal of  <100 mg/dL  as compared to ezetimibe (61.0 percent vs. 10 percent, respectively). Also of note, 50 percent of alirocumab patients did not need a dose increase to 150 mg at week 12. Alirocumab was also better tolerated than atorvastatin (HR ATV vs. ALI = 1.63 (95 percent CI: 1.01 to 2.62), nominal P=0.042). Fewer patients indicated skeletal muscle-related symptoms like myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness, and muscle fatigue with alirocumab than with atorvastatin and ezetimibe.

In addition to the ODYSSEY ALTERNATIVE trial, several other ODYSSEY trials were presented on Nov. 19 as part of the final day of AHA 2014. In the ODYSSEY HIGH FH trial, the LDL-C-lowering efficacy and safety of alirocumab was compared to placebo in patients with severe heterozygous familial hypercholesterolemia (heFH) and very high baseline levels of LDL-C despite maximally tolerated statin ± other lipid lowering therapy.  Overall results showed alirocumab significantly reduced LDL-C after 24 weeks of treatment compared to placebo. Alirocumab was also generally well tolerated and treatment-emergent adverse events (TEAEs) were generally comparable between the two groups.

The ODYSSEY LONG TERM trial, the largest double-blind study of a PCSK9 inhibitor, provided a closer look at the long-term safety, tolerability and efficacy of alirocumab in patients with high cardiovascular risk. According to study investigators, self-administered alirocumab produced significantly greater LDL-C reductions vs. placebo at week 24 (LS mean difference of 62 percent), with 79 percent of alirocumab patients achieving LDL-C of <70 mg/dL. TEAEs were generally comparable in alirocumab and placebo patients. 

ODYSSEY OPTIONS I and II focused on the efficacy and safety of combining alirocumab with atorvastatin or rosuvastatin, compared to adding ezetimibe, doubling statin dose or switching statin therapy in patients at high cardiovascular risk not achieving LDL-C levels of <70 mg/dL or <100 mg/dL. According to study investigators, self-administered alirocumab as an add-on to either atorvastatin (20 or 40 mg) or rosuvastatin (10 mg) produced significantly greater LDL-C reductions at week 24 compared to the other options. They also noted that 60 percent of patients receiving alirocumab achieved LDL-C <70 mg/dL at week 24, and >79 percent did not require a dose increase to alirocumab 150 mg. Safety and tolerability were comparable between trial groups.

Finally, the ODYSSEY COMBO I study offered a closer look at alirocumab in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia on maximally tolerated doses of statins. Similar to results from other ODYSSEY studies, self-administered alirocumab significantly reduced LDL-C from baseline at week 24 (48 percent vs. 2 percent placebo; P<0.0001). This reduction was maintained through 52 weeks. Study investigators noted that the “treat-to-target” approach with alirocumab resulted in 83 percent of patients not requiring a dose increase to 150 mg at week 12 and a majority of patients achieving LDL-C <70 mg/dL at week 24. The results “suggest safety and efficacy of a 75mg/150mg Q2W alirocumab treatment algorithm,” the investigators said. 

Clinical Topics: Dyslipidemia, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia, Statins

Keywords: Fluorobenzenes, Spasm, Muscle, Skeletal, Hyperlipoproteinemia Type II, Pyrimidines, Muscle Weakness, Risk Factors, Heptanoic Acids, Hypercholesterolemia, Muscle Fatigue, Pyrroles, Azetidines, Cardiovascular Diseases, Maximum Tolerated Dose, Sulfonamides, Myalgia

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