The European Commission ( EC ) has approved a new indication for Praluent ( Alirocumab ), to reduce cardiovascular ( CV ) risk in adults with established atherosclerotic CV disease ( ASCVD ) by lowering low-density lipoprotein cholesterol ( LDL-C ) levels as an adjunct to correction of other risk factors.
ASCVD is an umbrella term, defined as a build-up of plaque in the arteries that can lead to reduced blood flow and a number of serious conditions such as stroke, peripheral artery disease and acute coronary syndrome ( ACS ), which includes myocardial infarction and unstable angina.
The EC approval is based on data from ODYSSEY OUTCOMES, a phase 3 cardiovascular outcomes trial that assessed the effect of adding Alirocumab to maximally-tolerated statins in 18,924 patients who had an ACS between 1-12 months ( median 2.6 months ) before enrolling in the trial.
Results from the ODYSSEY OUTCOMES trial were published in The New England Journal of Medicine ( NEJM ) in 2018.
The trial met its primary endpoint, showing that Alirocumab significantly reduced the relative risk of major adverse CV events ( MACE ) by 15% in patients who had suffered a recent ACS.
MACE occurred in 903 patients ( 9.5% ) in the Alirocumab group and in 1,052 patients ( 11.1% ) in the placebo group ( hazard ratio, HR 0.85; 95% CI, 0.78 to 0.93; p less than 0.001 ).
Additionally, Alirocumab was associated with a 15% lower risk of death from any cause; which occurred in 334 ( 3.5% ) patients in the Alirocumab group and 392 ( 4.1% ) patients in the placebo group ( HR 0.85; 95% CI, 0.73 to 0.98; nominal significance ).
Adverse events were similar between the Alirocumab and placebo groups, except for injection site reactions ( Alirocumab 3.8%, placebo 2.1% ).
Praluent is the only PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor available in two starting doses as a single 1 milliliter ( mL ) injection ( 75 mg and 150 mg ) once every two weeks and can also be administered as 300 mg once every four weeks ( monthly ), enabling physicians to tailor treatment based on an individual patient’s LDL-Clowering needs.
In the ODYSSEY OUTCOMES trial patients were randomized to receive Alirocumab ( n=9,462 ) or a placebo ( n=9,462 ) and were assessed for a median of 2.8 years, with some patients being treated for up to 5 years. Approximately 90% of patients were on a high-intensity statin.
The trial was designed to maintain patients' LDL-C levels between 25-50 mg/dL ( 0.65- 1.29 mmol/L ), using two different doses of Alirocumab ( 75 mg and 150 mg) .
Alirocumab-treated patients started the trial on 75 mg every 2 weeks and switched to 150 mg every 2 weeks if their LDL-C levels remained above 50 mg/dL ( 1.29 mmol/L ) ( n=2,615 ).
Some patients who switched to 150 mg switched back to 75 mg if their LDL-C fell below 25 mg/dL ( 0.65 mmol/L ) ( n=805 ), and patients who experienced two consecutive LDL-C measurements below 15 mg/dL ( 0.39 mmol/L ) while on the 75 mg dose ( n=730 ) stopped active Alirocumab therapy for the remainder of the trial.
Alirocumab inhibits the binding of PCSK9 to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells to clear LDL, which lowers LDL-C levels in the blood. ( Xagena )
Source: Sanofi, 2019