The 18-month ( 78-week ) results of a phase 3 trial of Alirocumab ( Praluent ), an investigational therapy, involving 2,341 high risk patients with hypercholesterolemia were published in The New England Journal of Medicine ( NEJM ).
In the ODYSSEY LONG TERM trial, Alirocumab 150 mg every two weeks reduced low-density lipoprotein cholesterol ( LDL cholesterol ) by an additional 62% at week 24 when compared to placebo, the primary efficacy endpoint of the study, with consistent LDL cholesterol lowering maintained over 78 weeks.
ODYSSEY LONG TERM evaluated Alirocumab 150 mg ( n=1,553 ) every two weeks compared to placebo ( n=788 ) in patients who were at high cardiovascular risk and who were receiving maximally-tolerated statin therapy with or without other lipid-lowering treatment.
The trial included patients with heterozygous familial hypercholesterolemia ( HeFH ) ( n=276 Alirocumab, n=139 placebo ). Patients received 78 weeks of treatment followed by an eight-week safety assessment. Patients self-administered a subcutaneous injection every two weeks via a pre-filled syringe.
At week 24, Alirocumab reduced LDL cholesterol from baseline by an additional 62% versus placebo ( p less than 0.001 ) when added to the current standard of care, which included maximally-tolerated statins.
Efficacy remained consistent throughout treatment, and at week 78 there was a 56% reduction from baseline in LDL cholesterol for Alirocumab versus placebo ( p less than 0.001 ).
At week 24, 81% of patients in the Alirocumab group achieved their pre-specified LDL cholesterol goal ( either 70 mg/deciliter [ mg/dL ] or 100 mg/dL depending on baseline cardiovascular risk ) compared to 8.5% for placebo ( p less than 0.001 ).
Adverse events occurred in 81% of Alirocumab and 83% of placebo patients, leading to discontinuation in 7.2% and 5.8% of patients, respectively.
Adverse reactions were similar between groups, apart from differences in injection site reactions ( 5.9% Alirocumab, 4.2% placebo ), myalgia ( 5.4% Alirocumab, 2.9% placebo ), neurocognitive events ( 1.2% Alirocumab, 0.5% placebo ), and ophthalmological events ( 2.9% Alirocumab, 1.9% placebo ).
In a 3,759-patient, pooled safety analysis of nine placebo-controlled Alirocumab studies, rates of skeletal muscle-related and neurocognitive events were generally balanced between Alirocumab and placebo.
At week 78, positively adjudicated pre-specified cardiovascular adverse effects ( including additional cardiovascular adverse effects beyond those in the pre-specified ODYSSEY OUTCOMES endpoint of major adverse cardiac events ) occurred in 4.6% and 5.1% of Alirocumab and placebo patients, respectively.
In a post hoc analysis using a pre-specified endpoint that included coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization, a lower rate of adjudicated major adverse cardiac events was observed in the Alirocumab group ( 27 of 1550 patients, 1.7% ) compared with the placebo group ( 26 of 788 patients, 3.3%; hazard ratio, HR=0.52; 95% CI, 0.31 to 0.90; nominal p=0.02 ).
The cumulative incidence curves diverged progressively over time.
ODYSSEY LONG TERM was not designed to evaluate cardiovascular outcomes. The number of cardiovascular events seen in the post hoc analysis was relatively small, which limits the ability to draw conclusions on the effects of Alirocumab on cardiovascular events.
The ongoing ODYSSEY OUTCOMES trial will evaluate the cardiovascular benefits of Alirocumab in approximately 18,000 patients over 5 years.
Alirocumab is an investigational fully human monoclonal antibody targeting PCSK9 ( proprotein convertase subtilisin/kexin type 9 ). ( Xagena )
Source: Sanofi, 2015