Regeneron and Sanofi Announce 18-Month Results of ODYSSEY LONG TERM Trial with Praluent

Regeneron Pharmaceuticals and Sanofi have announced that 18-month (78-week) results of a Phase III trial of Praluent (alirocumab), an investigational therapy, involving 2,341 high risk patients with hypercholesterolemia were published online in The New England Journal of Medicine. In the ODYSSEY LONG TERM trial, Praluent 150 mg every 2 weeks reduced low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) by an additional 62% at week 24 when compared to placebo, the primary efficacy endpoint of the study, with consistent LDL-C lowering maintained over 78 weeks.

"These results demonstrated the durable efficacy for Praluent when added to maximally-tolerated statin therapy and further reinforce its generally consistent safety profile," said Jennifer Robinson, Director of the Prevention Intervention Center, Professor, Departments of Epidemiology & Medicine, College of Public Health at the University of Iowa. "Additionally, the post hoc analysis of major cardiovascular events represents an important finding for Praluent — we look forward to results from the ongoing ODYSSEY OUTCOMES trial, which is prospectively evaluating the potential of Praluent to reduce cardiovascular events."

18-Month (78-Week) Safety and Efficacy Results

ODYSSEY LONG TERM evaluated Praluent 150 mg (n=1,553) every 2 weeks compared to placebo (n=788) in patients who were at high cardiovascular (CV) risk and who were receiving maximally-tolerated statin therapy with or without other lipid-lowering treatment. The trial included patients with heterozygous familial hypercholesterolemia (HeFH) (n=276 Praluent, n=139 placebo). Patients received 78 weeks of treatment followed by an 8-week safety assessment. Patients self-administered a subcutaneous injection every 2 weeks via a pre-filled syringe. Key results include

• At week 24, Praluent reduced LDL-C from baseline by an additional 62% versus placebo (p less than 0.0001) when added to the current standard of care, which included maximally-tolerated statins.
• Efficacy remained consistent throughout treatment, and, at week 78 there was a 56% reduction from baseline in LDL-C for Praluent versus placebo (p less than 0.0001).
• At week 24, 81% of patients in the Praluent group achieved their pre-specified LDL-C goal (either 70 mg/deciliter [mg/dL] or 100 mg/dL depending on baseline CV risk) compared to 8.5% for placebo (p less than 0.0001).
• Adverse events (AEs) occurred in 81% of Praluent and 83% of placebo patients, leading to discontinuation in 7.2% and 5.8% of patients, respectively. AEs were similar between groups, apart from differences in injection site reactions (5.9% Praluent, 4.2% placebo), myalgia (5.4% Praluent, 2.9% placebo), neurocognitive events (1.2% Praluent, 0.5% placebo), and ophthalmological events (2.9% Praluent, 1.9% placebo). In a 3759-patient, pooled safety analysis of nine placebo-controlled Praluent studies to be presented on Monday, 16 March at ACC.15, rates of skeletal muscle-related and neurocognitive events were generally balanced between Praluent and placebo.
• At week 78, positively adjudicated pre-specified CV adverse events (including additional CV AEs1 beyond those in the pre-specified ODYSSEY OUTCOMES endpoint of 'major adverse cardiac events' described below) occurred in 4.6% and 5.1% of Praluent and placebo patients, respectively. 
• In a post hoc analysis using a pre-specified endpoint that included coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization, a lower rate of adjudicated major adverse cardiac events was observed in the Praluent group (27 of 1550 patients, 1.7%) compared with the placebo group (26 of 788 patients, 3.3%; hazard ratio 0.52; 95% CI, 0.31 to 0.90; nominal p less than 0.01). The cumulative incidence curves diverged progressively over time.
• ODYSSEY LONG TERM was not designed to evaluate CV outcomes. The number of CV events seen in the post hoc analysis was relatively small, which limits the ability to draw conclusions on the effects of Praluent on CV events. The ongoing ODYSSEY OUTCOMES trial will evaluate the CV benefits of Praluent in approximately 18,000 patients over 5 years.