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New Phase III Data for Cholesterol-Lowering Drug Alirocumab (Praluent)

Treatment reduces LDL-C in four late-stage trials

In a new pooled analysis of patients with heterozygous familial hypercholesterolemia (HeFH) included in the phase III ODYSSEY clinical trial program, alirocumab (Praluent, Regeneron Pharmaceuticals/Sanofi) was able to significantly lower “bad” low-density lipoprotein cholesterol (LDL-C).

At week 24, when the primary efficacy endpoint was assessed, patients treated with alirocumab had an average 56% greater reduction in LDL-C compared with placebo (P < 0.0001) in both treatment arms (75 mg and 100 mg). The reductions in LDL-C were observed as early as week 4 and were maintained for the duration of therapy (until week 78).

The results of this analysis were presented at the European Society of Cardiology (ESC) Congress 2015 in London, and the 78-week results from two of the four trials included in the analysis, ODYSSEY FH I and II, were concurrently published online in the European Heart Journal.

People with HeFH have an inherited form of high cholesterol and are unable to process the body’s natural supply of cholesterol in the liver, leading to very high levels of LDL-C that can result in atherosclerosis, which in turn can lead to a heart attack or stroke. If untreated, people with HeFH typically have LDL-C levels of 200 to 400 mg/dL, are at high risk for premature atherosclerosis and cardiovascular (CV) events, and are at 20 times greater risk of developing heart disease.

The analysis presented at the ESC meeting evaluated the efficacy and safety of alirocumab compared with placebo in 1,257 patients with HeFH. Data from four phase III ODYSSEY trials –– LONG TERM (HeFH patients only), HIGH FH, FH I, and FH II –– were included in the analysis. In these studies, patients received either alirocumab or placebo in addition to standard of care, which included maximally tolerated statins with or without other lipid-lowering therapies, such as ezetimibe.

In the LONG TERM and HIGH FH studies, patients were treated with alirocumab 150 mg (n = 348) every 2 weeks administered as a single 1-mL injection or placebo (n = 174). The average LDL-C level at baseline was 168 mg/dL and 162 mg/dL in the alirocumab and placebo groups, respectively. In the FH I and FH II trials, the patients were treated with alirocumab 75 mg (n = 490) every 2 weeks administered as a single 1-mL injection or placebo (n = 245). In FH I and FH II, patients had their doses adjusted to 150 mg at week 12 if they did not achieve their prespecified LDL-C goal at week 8. In these patients, the average LDL-C level at baseline was 141 mg/dL in both the alirocumab and placebo groups.

Across all primary and secondary endpoints assessed, the investigators observed statistical differences in favor of alirocumab compared with placebo. Patients treated with alirocumab achieved average LDL-C levels of less than 85 mg/dL at week 12 and maintained these levels through 78 weeks of therapy.

Seventy-five percent of the patients initially treated with 75 mg of alirocumab achieved the LDL-C goal at week 24 compared with 5% of the placebo group. Similarly, 65% of the patients initially treated with 150 mg of alirocumab achieved the LDL-C goal compared with 4% of placebo-treated patients.

Alirocumab, a human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), is approved for use in the U.S. as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical atherosclerotic CV disease who require additional lowering of LDL-C. The effect of alirocumab on CV morbidity and mortality has not been determined

Source: Regeneron Pharmaceuticals; September 1, 2015.


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