The phase III ODYSSEY MONO trial testing alirocumab monotherapy, an investigational antibody targeting PCSK9, met its primary efficacy endpoint, announced Sanofi and Regeneron Pharmaceuticals on Wednesday 16 October. The primary efficacy endpoint of mean LDL-c reduction from baseline to week 24 was significantly greater in patients randomised to alirocumab, as compared to patients who were randomised to ezetimibe (42.7% vs. 15.6%, P<0.0001).

ODYSSEY MONO was a randomised, double-blind, active-controlled, parallel-group study (n=103) that evaluated the efficacy and safety of alirocumab over 24 weeks in patients with primary hypercholesterolemia and moderate cardiovascular risk. Patients were randomised to monotherapy with either ezetimibe 10 mg, or alirocumab. Alirocumab was self-administered at 75 mg every two weeks, and up-titrated to 150 mg at week 12 if LDL-c was above 70 mg/dL at week 8. The majority of patients remained on the initial low dose of alirocumab of 75 mg. Self-administration was done subcutaneously with a single-use 1 mL auto-injector.

78.4% of patients on ezetimibe and 69.2% of patients receiving alirocumab reported treatment-emergent adverse events. Infections were most common (39.2% with ezetimibe vs. 42.3% with alirocumab), including nasopharyngitis, influenza and upper respiratory tract infection. Injection-site reactions occurred in less than 2% of patients in both treatment groups. Muscle-related adverse events were documented in 3.9% of patients on ezetimibe and 3.8% of patients treated with alirocumab.

Three years ago, the first phase 1 trials showed that blocking PCSK9 could lower cholesterol levels in humans. The ODYSSEY MONO trial data represent the first phase III data for this promising potential new class of lipid-lowering agents. These are the first data of an extensive ODYSSEY phase III program, including trials investigating alirocumab in combination with other lipid-lowering therapies.

Source: press release Sanofi 16/10/2013