Alirocumab Effective in Hypercholesterolemia 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 150 mg every 2 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 prespecified 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 levels in the alirocumab group as compared to a 1% increase in the placebo group (62% reduction in alirocumab group compared to placebo) (P<.0001).
• At 52 weeks, there was a 57% reduction from baseline in LDL levels in the alirocumab group as compared to a 4% increase in the placebo group (61% reduction in alirocumab group compared with placebo), (P<.0001).
• 81% of alirocumab patients achieved their prespecified LDL goal (either 70 mg/dL or 100 mg/dL depending on patients’ baseline CV risk) compared with 9% for placebo (P<.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 with placebo (1.4% compared to 3.0%, nominal P<.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.

In the three additional trials, ODYSSEY COMBO II, FH I and FH II, alirocumab-treated patients receive an initial dose of alirocumab 75 mg every 2 weeks, increasing to 150 mg if needed to reach prespecified LDL levels.

ODYSSEY COMBO II is a double blind trial designed to evaluate the safety and efficacy of alirocumab compared with zetimibe in patients (n=720) with hypercholesterolemia who are at high CV risk and had inadequate LDL 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 levels in the alirocumab group compared to a 21% reduction in the ezetimibe group (30% reduction in alirocumab group compared to ezetimibe group), (P<.0001).
• At 52 weeks, there was a 50% reduction from baseline in LDL levels in the alirocumab group compared to an 18% reduction in the ezetimibe group (32% reduction in alirocumab group compared to ezetimibe group), (P<.0001).
• 77% of patients in the alirocumab group achieved an LDL 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 levels of 145 mg/dL (FH I) and 134 mg/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 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 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 goal (either 70 mg/dL or 100 mg/dL) at 24 weeks compared to 2% and 11% in the placebo groups, respectively (P<.0001). Approximately 50% of patients in the alirocumab groups remained on the 75mg dose.

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

This article originally appeared on MPR