FDA approves new PCSK9 inhibitor to lower LDL Cholesterol and CVD risk

The U.S. Food and Drug Administration (FDA) has approved Praluent^® (alirocumab) to reduce the risk of heart attack, stroke and unstable angina requiring hospitalization in adults with established cardiovascular (CV) disease. The FDA approval is based on data from ODYSSEY OUTCOMES, which was published in the New England Journal of Medicine in November 2018.

High levels of low-density lipoprotein cholesterol or LDL cholesterol (LDL-C), increase patients' risk for serious CV events such as heart attack or stroke. Adults who experience a heart attack or stroke have approximately one in three chance to have another CV event.

"Heart disease accounts for one-quarter of all American deaths each year and many others are at risk for heart attack and stroke due to uncontrolled LDL-C levels," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer, Regeneron. "The Phase 3 ODYSSEY OUTCOMES trial showed that people who received Praluent significantly reduced their risk for serious cardiovascular events. There was also a clinically meaningful reduction in death from any cause with Praluent treatment. With this approval and the recent introduction of a lower U.S. Praluent list price, we hope that more patients in need will be able to access Praluent."

"Today's FDA approval marks a significant achievement in the treatment of adults with established cardiovascular disease, who are among those at greatest risk of death or disability caused by serious cardiovascular events," said John Reed, M.D., Ph.D., Global Head of Research & Development, Sanofi. "Praluent has already helped many adults lower their LDL-C levels, and this new indication provides an opportunity to help appropriate patients by reducing the risk of serious, life-threatening cardiovascular events, including heart attacks and stroke."

The data from ODYSSEY OUTCOMES assessed the effect of adding Praluent to maximally-tolerated statins on CV outcomes in 18,924 patients who had acute coronary syndrome (ACS) within a year of enrolling in the trial. Patients who received Praluent in the trial experienced:

• A 15% reduced risk for major CV events. The primary endpoint included time to first heart attack, stroke, death from coronary heart disease (CHD), or unstable angina requiring hospitalization (HR 0.85; 95% CI, 0.78 to 0.93; p=0.0003).


• A 27% reduced risk of stroke, 14% reduced risk of non-fatal heart attack and 39% reduced risk of unstable angina requiring hospitalization.*


• A 15% reduced risk of death from any cause (also called all-cause mortality; HR 0.85; 95% CI, 0.73 to 0.98; nominal p=0.026) was also observed.*

*Because statistical testing of these endpoints was performed outside of the hierarchy, the results are not considered statistically significant.

Adverse events were similar between the Praluent and placebo groups, except for injection site reactions (Praluent 3.8%, placebo 2.1%). In ODYSSEY OUTCOMES, the adverse events that occurred in >5% of patients included: non-cardiac chest pain (7.0% Praluent, 6.8% placebo), nasopharyngitis (6.0% Praluent, 5.6% placebo) and myalgia (5.6% Praluent, 5.3% placebo).

The FDA also approved Praluent as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-C.

Praluent was the first PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor approved by the FDA and is the only PCSK9 inhibitor available in two doses with two levels of efficacy as a single 1 mL injection (75 mg and 150 mg) once every two weeks. It can also be administered as 300 mg once every four weeks (monthly), enabling physicians to tailor treatment based on an individual patient's LDL-C-lowering needs.