A new pooled analysis of heterozygous familial hypercholesterolaemia (HeFH) patients included in the ODYSSEY clinical trial programme found that alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C).
The results were announced at the 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.
The analysis included 1,257 HeFH patients, the largest group of HeFH patients ever studied in a Phase 3 program. At week 24, when the primary efficacy endpoint was assessed, patients treated with alirocumab had an average 56% greater reduction in LDL-C compared to placebo (p<0.0001) in both arms. Reductions were observed as early as week four and were maintained for the duration of therapy, until week 78.
“Approximately 20% of HeFH patients achieve LDL-C less than 100mg/dL with statins. In this analysis, up to 75% of patients who added alirocumab to standard-of-care achieved their LDL-C goals by week 24,” said John J.P. Kastelein, Professor of Medicine, Department of Vascular Medicine, Academic Medical Center/University of Amsterdam, the Netherlands. “Both alirocumab 75mg and 150mg significantly reduced LDL-C levels below 100 mg/dL and sustained these lower levels through 78 weeks, offering patients and their doctors a flexible approach to treatment, with adverse events comparable to placebo.”
Across the pooled analysis, the most common adverse events (occurring in at least 5% of patients in any alirocumab group) were nasopharyngitis, injection site reaction, influenza, headache, upper respiratory tract infection, arthralgia, back pain, urinary tract infection, and myalgia.
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 block arteries (atherosclerosis) and can lead to a heart attack or stroke. If left untreated, people with HeFH typically have LDL-C levels of 200-400 milligrams/deciliter (mg/dL), are at high risk for premature atherosclerosis and cardiovascular (CV) events, and at 20 times greater risk of developing heart disease.
The analysis presented at ESC Congress 2015 evaluated the efficacy and safety of alirocumab compared to placebo in 1,257 patients with HeFH. Data from four Phase 3 ODYSSEY trials, LONG TERM (HeFH patients only), HIGH FH, FH I, and FH II, were included in the analysis. In these trials, patients either received alirocumab or placebo, in addition to standard-of-care, which included 2/4 maximally-tolerated statins with or without other lipid-lowering therapies such as ezetimibe.
In ODYSSEY LONG TERM and HIGH FH, patients were treated with alirocumab 150 mg (n=348) every two weeks administered as a single 1-milliliter (mL) injection or placebo (n=174). In these patients, the average LDL-C at baseline was 168 mg/dL and 162 mg/dL in the alirocumab and placebo groups respectively. In ODYSSEY FH I and FH II, patients were treated with alirocumab 75mg (n=490) every two weeks administered as a single 1-mL injection or placebo (n=245). In ODYSSEY FH I and FH II, patients had their dose adjusted to 150mg at week 12 if they did not achieve their pre-specified LDL-C goal at week eight. In these patients, the average LDL-C level at baseline was 141mg/dL in both the alirocumab and placebo groups.