New injectable antibody alirocumab enhances lipid-lowering effect of statins

In clinical trials alirocumab was associated with a mean reduction in LDL-C of up to 61% in patients already taking statins and up to 47% in those not on statins.

Further information
View Praluent drug record 
Summary of Product Characteristics
Manufacturer: Sanofi

Alirocumab is a human IgG1 monoclonal antibody that binds to the PCSK9 (proprotein convertase subtilisin kexin type 9) enzyme, preventing PCSK9-mediated degradation of LDL receptors on the surface of liver cells. This leads to an increase in the number of receptors available to clear LDL, thereby decreasing levels of LDL-C.

Self-administration

Praluent is given as a subcutaneous injection into the thigh, abdomen or upper arm once every two weeks. It is supplied as a prefilled pen and patients may self-inject once they have received appropriate training from a healthcare professional.

Praluent is indicated for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

• in combination with a statin with or without other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or
• alone or in combination with other lipid-lowering therapies in patients for whom statins are contraindicated or not tolerated

Clinical trial programme

The efficacy of alirocumab is being evaluated in a number of clinical trials forming the Odyssey Program. Five of the studies which have been completed and fully published involved over 3,800 patients with hypercholesterolaemia or mixed dyslipidaemia.

In four of these studies patients were taking a maximally tolerated dose of statin with or without other lipid-modifying therapies and were at high or very high cardiovascular risk. Patients in the fifth study (ODYSSEY MONO) were at moderate cardiovascular risk and were not taking statins or other lipid-lowering therapies.

The primary efficacy endpoint for all the trials was the mean percent reduction from baseline in LDL-C at week 24 compared with placebo or ezetimbe. All of the studies met their primary endpoint:

• ODYSSEY COMBO I (n=316) compared alirocumab* with placebo (48.2% vs 2.3%, respectively [p<0.0001])
• ODYSSEY COMBO II (n=720) compared alirocumab* with ezetimibe 10mg daily orally (50.6% vs 20.7%, respectively [p<0.0001])
• ODYSSEY MONO (n=103) compared alirocumab* with ezetimibe 10mg daily, both as monotherapy (47% vs 16%, respectively [p<0.0001])
• ODYSSEY LONG TERM (n=2,341) compared alirocumab (150mg every two weeks) with placebo (61% vs 0.8%, respectively [p<0.001]) 
• ODYSSEY OPTIONS I included 355 patients on a baseline regimen of atorvastatin 20mg or 40mg who were randomised to add-on alirocumab*, ezetimibe 10mg daily, doubling of atorvastatin dose, or a switch to rosuvastatin 40mg daily (atorvastatin 40mg group only). In the atorvastatin 20mg and 40mg groups, respectively, add-on alirocumab reduced LDL-C by 44.1% and 54.0% (p<0.001 vs all comparators).

*alirocumab dose: 75mg every two weeks increasing to 150mg at week 12 if week 8 LDL-C ≥70mg/dl.

Ongoing trials

The ODYSSEY OUTCOMES trial is an ongoing study investigating the ability of alirocumab to reduce the occurrence of cardiovascular events with results anticipated in 2017. A number of other trials are also ongoing (see Odyssey Program).

Well tolerated

Alirocumab was well tolerated in clinical trials with upper respiratory tract signs and symptoms, pruritus and injection site reactions the most commonly reported adverse events.