Sanofi and Regeneron Pharmaceuticals have announced that the Phase 3 ODYSSEY MONO trial with Alirocumab, an investigational monoclonal antibody targeting PCSK9 ( proprotein convertase subtilisin/kexin type 9 ), met its primary efficacy endpoint.
The mean low density lipoprotein-cholesterol ( LDL-C ) reduction from baseline to week 24, the primary efficacy endpoint of the study, was significantly greater in patients randomized to Alirocumab, as compared to patients randomized to Ezetimibe ( Ezetrol, Zetria ) ( 47.2% vs. 15.6%, p less than 0.0001 ).
In the trial, which employed a dose increase ( up-titration ) for patients who did not achieve an LDL-C level of 70 milligrams/deciliter ( mg/dL ), the majority of patients remained on the initial low dose of Alirocumab of 75 mg.
The percentage of patients who reported treatment emergent adverse events was 78.4% in the Ezetimibe group and 69.2% in the Alirocumab group.
The most common class of adverse events was infections ( 39.2% with Ezetimibe vs. 42.3% with Alirocumab ), which included nasopharyngitis, influenza, and upper respiratory tract infection.
Injection-site reactions occurred in less than 2% of patients in both groups.
Muscle-related adverse events occurred in 3.9% of patients treated with Ezetimibe and 3.8% of patients treated with Alirocumab.
ODYSSEY MONO is the first study to report data from the 12 Phase 3 trials that have been initiated so far as part of the more than 23,000 patient ODYSSEY clinical trial program.
ODYSSEY MONO ( n=103 ) was a randomized, double-blind, active-controlled, parallel-group study to evaluate the efficacy and safety of Alirocumab over 24 weeks in patients with primary hypercholesterolemia and moderate cardiovascular risk.
Patients in the trial were randomized to receive monotherapy with either Ezetimibe 10 mg, or Alirocumab.
Alirocumab was self-administered initially at its low dose of 75 mg every two weeks, and was up-titrated at week 12 to 150 mg if the LDL-C measurement at week 8 was above 70 mg/dL. The majority of Alirocumab patients in the trial remained on the initial low dose of Alirocumab because they achieved LDL-C below 70 mg/dL at week 8.
Alirocumab was self-administered subcutaneously using a single-use 1 mL auto-injector.
PCSK9 is known to be a determinant of circulating LDL levels, as it binds to LDL receptors resulting in their degradation so that fewer are available on liver cells to remove excess LDL-cholesterol from the blood.
Moreover, traditional LDL-lowering therapies such as statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-cholesterol.
Blocking the PCSK9 pathway is therefore a potentially novel mechanism for lowering LDL-cholesterol.
Alirocumab is an investigational, fully-human monoclonal antibody that targets and blocks PCSK9. It is administered via subcutaneous injection. By inhibiting PCSK9 Alirocumab has been shown in pre-clinical studies to increase the number of LDL receptors on hepatocytes, thereby lowering LDL cholesterol. ( Xagena )
Source: Sanofi, 2013