Sanofi, a global healthcare leader, and Regeneron Pharmaceuticals, Inc., a leading science-based biopharmaceutical company, announced that in a new pooled analysis of heterozygous familial hypercholesterolemia (HeFH) patients included in the ODYSSEY clinical trial programme, Praluent (alirocumab) significantly reduced bad cholesterol, known as low-density lipoprotein cholesterol (LDL-C).
This analysis included 1,257 HeFH patients, the largest group of HeFH patients ever studied in a phase 3 programme. At week 24, when the primary efficacy endpoint was assessed, patients treated with Praluent had an average 56 per cent greater reduction in LDL-C compared to placebo (p<0.0001) in both arms. Reductions were observed as early as week 4 and were maintained for the duration of therapy, until week 78.
Results of this analysis were presented 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.
"Approximately 20 percent of HeFH patients achieve LDL-C less than 100 mg/dL with statins. In this analysis, up to 75 per cent of patients who added Praluent to standard-of-care achieved their LDL-C goals by week 24," said John J.P. Kastelein, M.D., Ph.D., FESC, professor of medicine, department of vascular medicine, Academic Medical Center/University of Amsterdam, Amsterdam.
"Both Praluent 75 mg and 150 mg 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 per cent of patients in any Praluent 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 Praluent 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 Praluent or placebo, in addition to standard-of-care, which included maximally-tolerated statins with or without other lipid-lowering therapies such as ezetimibe. In ODYSSEY LONG TERM and HIGH FH, patients were treated with Praluent 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 Praluent and placebo groups respectively. In ODYSSEY FH I and FH II, patients were treated with Praluent 75 mg (n=490) every two weeks administered as a single 1-ml injection or placebo (n=245).1 In ODYSSEY FH I and FH II, patients had their dose adjusted to 150 mg at week 12 if they did not achieve their pre-specified LDL-C goal at week 8. In these patients, the average LDL-C level at baseline was 141 mg/dL in both the Praluent and placebo groups.
Across all primary and secondary endpoints assessed, there were statistical differences in favor of Praluent compared to placebo. Patients treated with Praluent achieved average LDL-C levels of less than 85 mg/dL at week 12,6 and maintained reductions through 78 weeks of therapy.1
Praluent, a human monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), is approved for use in the US as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical atherosclerotic CV disease (ASCVD), who require additional lowering of LDL-C. The effect of Praluent on CV morbidity and mortality has not been determined. In July, the European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of Praluent in certain adult patients with hypercholesterolemia, and a final decision from the European Commission is anticipated in September.