18-month results of ODYSSEY LONG TERM trial with Praluent (alirocumab) announced

Sanofi and Regeneron Pharmaceuticals, Inc. have announced that 18-month (78-week) results of a Phase 3 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 two weeks reduced low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) by an additional 62 percent 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, M.D., M.P.H., 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 two 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 eight-week safety assessment. Patients self-administered a subcutaneous injection every two weeks via a pre-filled syringe. Key results include:

• At week 24, Praluent reduced LDL-C from baseline by an additional 62 percent versus placebo (p<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 percent reduction from baseline in LDL-C for Praluent versus placebo (p<0.0001).
• At week 24, 81 percent 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 percent for placebo (p<0.0001).
• Adverse events (AEs) occurred in 81 percent of Praluent and 83 percent of placebo patients, leading to discontinuation in 7.2 percent and 5.8 percent of patients, respectively. AEs were similar between groups, apart from differences in injection site reactions (5.9 percent Praluent, 4.2 percent placebo), myalgia (5.4 percent Praluent, 2.9 percent placebo), neurocognitive events (1.2 percent Praluent, 0.5 percent placebo), and ophthalmological events (2.9 percent Praluent, 1.9 percent placebo). In a 3,759-patient, pooled safety analysis of nine placebocontrolled Praluent studies to be presented on Monday, rates of skeletal muscle-related and neurocognitive events were generally balanced between Praluent and placebo.
• At week 78, positively adjudicated pre-specified CV AEs (including additional CV AEs1 beyond those in the pre-specified ODYSSEY OUTCOMES endpoint of 'major adverse cardiac events' described below) occurred in 4.6 percent and 5.1 percent 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 percent) compared with the placebo group (26 of 788 patients, 3.3 percent; hazard ratio 0.52; 95 percent 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.

Praluent ACC.15 Presentation Highlights

• Positive results from the ODYSSEY CHOICE I and CHOICE II trials, which evaluated monthly dosing of Praluent 300 mg and Praluent 150 mg, were presented at the American College of Cardiology's 64th Annual Scientific Sessions & Expo (ACC.15), in San Diego. The full poster presentation is available on Regeneron's website here.
• On Monday, investigators will present a pooled analysis of AEs from five Phase 3 and four Phase 2 double-blind, placebo-controlled trials exploring multiple Praluent doses and regimens involving 3,759 patients with hypercholesterolemia who also received statins. These slides will be available on Monday on Regeneron's website.

Praluent is an investigational fully human monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9). Earlier this year, Regeneron and Sanofi announced that the Biologics License Application (BLA) for Praluent was accepted for priority review by the U.S. Food and Drug Administration (FDA). Under the Prescription Drug User Fee Act (PDUFA), the goal for a priority review is six months, for a target action date of July 24, 2015. Additionally, the European Medicines Agency (EMA) accepted for review the Marketing Authorization Application for Praluent in the European Union. The EMA and FDA have conditionally accepted Praluent as the trade name for alirocumab. The safety and efficacy of Praluent have not been fully evaluated by any regulatory authority.

Further details of the presentation can be found on Regeneron's website.