FDA Accepts Alirocumab sBLA for MACE Risk Reduction

The US Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for alirocumab (Praluent) as a preventive therapy in overall major adverse cardiovascular event (MACE) risk.

The proprotein convertase subtilsin-kexin type 9 (PCSK9) inhibitor from Sanofi and Regeneron Pharmaceuticals was the first of its drug class to be approved for the treatment of high LDL-cholesterol (LDL-C) in adjunction with diet and statin therapy, in June 2015. This new indication clears it to help reduce patient risk of heart attack, ischemic stroke, fatal coronary heart disease, and hospitalization from unstable angina.

Alirocumab’s sBLA was supported by data to come from the phase 3 ODYSSEY OUTCOMES trial, an approximate 19,000-patient study assessing the therapy in patients with acute coronary syndrome (ACS) within 1-12 months prior to enrollment.

The results showed patients administered alirocumab had a 15% reduced risk (HR .85; 95% CI: .78-.93; P= .0003) in MACE over 4 years. Overall, MACE occurred in 9.5% (n= 903) of treated patients, versus 11.1% (1052) of those administered placebo.

Patients also reported tolerance to alirocumab, with just 3.8% (360) of patients reporting a local injection site reaction, compared to 2.1% (203) of patients on placebo.

Investigators also reported a 15% reduced risk of death from any cause, though the findings were not statistically significant.

In discussing the significance of the MACE reduction findings, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, noted that heart disease occurs in approximately one-fourth of all Americans annually. Alirocumab's capability to both reduce the risk of a MACE—and possibly, a patient's mortality to one that occurs—is critical to this population.

"With this approval, and the recent introduction of a lower US Praluent list price, we hope that more patients in need will be able to access Praluent," he said in a statement.

One year following the trial results, Wouter Jukema, MD, PhD, professor of Cardiology at Leiden University Medical Center in The Netherlands, spoke with MD Magazine® at the American College of Cardiology (ACC) 2019 Annual Meeting . The ODYSSEY OUTCOMES sub-study author explained that overly positive patient adherence rates in a real-world setting came as a surprise even to alirocumab investigators.

“People easily stop ingesting pills, but injections were very well tolerated, and patients didn't bother at all,” he explained. “On the contrary, we had the idea that finally, something really good was done. Adherence was really excellent.”

Earlier this year, the FDA approved an update to Praluent’s prescribing information to include clinical information regarding its use in patients with heterozygous familial hypercholesterolemia (HeFH), an inherited form of high cholesterol, who require additional LDL-C and are undergoing aphersesis treatment. The update was supported by the phase ODYSSEY ESCAPE trial data of 62 patients with HeFH.

This new sBLA, though, could have significant implications for critically at-risk patients, John Reed, MD, PhD, global head of Research & Development at Sanofi, said in a statement.

"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," Reed said.