European Commission approves Praluent (alirocumab) to treat LDL cholesterol in hypercholesterolemia patients- Sanofi + Regeneron

Sanofi and Regeneron Pharmaceuticals announced that the European Commission (EC) has granted marketing authorisation for Praluent (alirocumab) for the treatment of low-density lipoprotein (LDL) cholesterol, in certain adult patients with hypercholesterolemia. Praluent is the only EC-approved PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor that is available in two starting doses as a single 1 mL injection (75 mg and 150 mg) once every two weeks, offering two levels of efficacy. Praluent will be available in a single-dose pre-filled pen that patients self-administer. The EC approved alirocumab for the treatment of adult patients with primary hypercholesterolemia (heterozygous familial hypercholesterolemia [HeFH]) and non-familial or mixed dyslipidemia as an adjunct to diet:

• a) in combination with a statin, or statin with other lipid-lowering therapies in patients unable to reach their LDL-cholesterol goals with the maximally-tolerated statin
• b) alone or in combination with other lipid-lowering therapies for patients who are statin intolerant, or for whom a statin is contraindicated.

The effect of alirocumab on cardiovascular (CV) morbidity and mortality has not yet been determined.

The EC marketing authorisation is based on data from 10 pivotal ODYSSEY trials, including five placebo-controlled and five ezetimibe-controlled studies. The data showed consistent, robust reductions in LDL-cholesterol for alirocumab compared to placebo or ezetimibe, when added to current standard-of-care, which included maximally-tolerated statins. All trials met their primary efficacy endpoint, demonstrating significantly greater reductions from baseline in LDL-cholesterol at week 24, compared to placebo or ezetimibe. In the placebo-controlled trials, the average LDL-cholesterol reductions from baseline at week 24 for the alirocumab group ranged from 46–61%. In the ezetimibe-controlled trial with alirocumab added to background statins, the average change in LDL-cholesterol from baseline was 51% at week 24. In the ezetimibe trials with patients not on statins, the average LDL-cholesterol reduction from baseline in the alirocumab group ranged from 45–47% at week 24. Additionally, significantly more patients achieved an LDL-cholesterol level of less than 70 mg/dL in the Praluent group compared to placebo or ezetimibe at week 12 and week 24.

Comment: Alirocumab is now the second drug in the PCSK9 inhibitor class to enter the EU market, following Amgen’s Repatha (evolocumab), which won approval in July 2015 for the same adult target group as well as in patients aged 12 years and older. Sanofi + Regeneron seek to differentiate alirocumab from evolocumab by its having two starting doses, offering two levels of efficacy which may contribute to tailored treatment.