Alirocumab Demonstrates Efficacy in Four Phase 3 Trials

Sanofi and Regeneron announced positive results from four Phase 3 ODYSSEY trials of alirocumab in patients with hypercholesterolemia. Alirocumab is an investigational monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9).

The double-blind ODYSSEY LONG TERM trial is designed to evaluate the long-term safety and efficacy of alirocumab 150mg every two weeks vs. placebo in patients (n=2,341) with hypercholesterolemia who are at high or very-high cardiovascular (CV) risk, including those heterozygous familial hypercholesterolemia (HeFH). Both study groups are treated with statins at a maximally-tolerated dose and some patients also receive additional lipid-lowering therapies. A pre-specified interim analysis was performed when all patients reached one year and approximately 25% of patients reached 18 months of treatment.

Key data includes:

• On the primary efficacy endpoint of the trial, at 24 weeks, there was a 61% reduction from baseline in LDL-C levels in the alirocumab group as compared to a 1% increase in the placebo group (62% reduction in alirocumab group compared to placebo) (P<0.0001).
• At 52 weeks, there was a 57% reduction from baseline in LDL-C levels in the alirocumab group as compared to a 4% increase in the placebo group (61% reduction in alirocumab group compared to placebo), (P<0.0001).
• 81% of alirocumab patients achieved their pre-specified LDL-C goal (either 70mg/dL or 100mg/dL depending on patients’ baseline CV risk) compared to 9% for placebo (P<0.0001).
• In a post hoc safety analysis, there was a lower rate of adjudicated major CV events (cardiac death, myocardial infarction, stroke, and unstable angina requiring hospitalization) in the alirocumab group compared to placebo (1.4% compared to 3.0%, nominal P<0.01). These CV events comprise the composite primary endpoint of the ongoing 18,000-patient ODYSSEY OUTCOMES trial, which is prospectively evaluating the potential of alirocumab to demonstrate CV benefit.

RELATED: Alirocumab Meets Primary Endpoint in Hypercholesterolemia Trials

In the three additional trials, ODYSSEY COMBO II, FH I and FH II, alirocumab-treated patients receive an initial dose of alirocumab 75mg every two weeks, increasing to 150mg if needed to reach pre-specified LDL-C levels.

ODYSSEY COMBO II is a double-blind trial designed to evaluate the safety and efficacy of alirocumab compared to ezetimibe in patients (n=720) with hypercholesterolemia who are at high CV risk and had inadequate LDL-C reduction at baseline despite stable maximally-tolerated statin therapy.

Key data includes:

• On the primary endpoint of the trial, at 24 weeks, there was a 51% reduction from baseline in LDL-C levels in the alirocumab group compared to a 21% reduction in the ezetimibe group (30% reduction in alirocumab group compared to ezetimibe group), (P<0.0001).
• At 52 weeks, there was a 50% reduction from baseline in LDL-C levels in the alirocumab group compared to an 18% reduction in the ezetimibe group (32% reduction in alirocumab group compared to ezetimibe group), (P<0.0001).
• 77% of patients in the alirocumab group achieved an LDL-C level of 70mg/dL at 24 weeks.
• Approximately 80% of patients in the alirocumab group remained on the initial 75mg alirocumab dose.

The ODYSSEY FH I and FH II trials enrolled a total of 738 HeFH patients and compare alirocumab to placebo. All patients are on maximally-tolerated daily statin therapy and the majority of patients also receive ezetimibe. Despite receiving this high level of background therapy, patients in these studies had mean baseline LDL-C levels of 145mg/dL (FH I) and 134mg/dL (FH II).

Key data includes:

• On the primary endpoint of the trials, at 24 weeks, there was a 49% reduction from baseline in LDL-C levels in both FH I and FH II alirocumab groups compared to an increase of 9% in FH I and 3% in FH II in the placebo groups (58% and 51% reduction compared to placebo), (P<0.0001).
• At 52 weeks, in FH I, there was a 47% reduction from baseline and, in FH II, a 50% reduction from baseline in LDL-C levels in the alirocumab groups compared to an increase of 9% and 8% in the placebo groups, respectively (56% and 58% reduction compared to placebo), (P<0.0001).
• 72% of alirocumab-treated patients in FH I, and 81% of alirocumab-treated patients in FH II, achieved their pre-specified LDL-C goal (either 70 mg/dL or 100 mg/dL) at 24 weeks compared to 2% and 11% in the placebo groups, respectively (P<0.0001). Approximately 50% of patients in the alirocumab groups remained on the 75mg dose.

For more information visit Sanofi.com or Regeneron.com.