Brand Name: Praluent
Generic Name: alirocumab
Drug Class: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor
Similar Drugs: Repatha (evolocumab)
Manufacturer: Sanofi and Regeneron
FDA Approval Date: July 24, 2015
What is Praluent and its mechanism of action?
Praluent belongs to a brand new class of drugs known as proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. Praluent is an antibody that targets PCSK9. Antibodies are proteins that attack foreign substances that invade the body by binding to them. Antibodies can also be designed in the lab to target substances that are native to the body as well (such as PCSK9). PCSK9 is a protein that reduces the number of receptors that remove cholesterol, such as LDL cholesterol, from the blood. LDL (low-density lipoprotein) cholesterol is commonly known as the “bad” cholesterol. When too much LDL cholesterol circulates in the blood it can slowly build up in the inner walls of the arteries. Thick, hard deposits (plaque) can narrow the arteries causing atherosclerosis. In addition, these plaques can detach and cause a heart attack or stroke. By blocking PCSK9, Praluent allows more receptors to be available to remove LDL cholesterol from the blood — resulting in decreased LDL levels and lower risk of forming dangerous plaques.
What are the uses for Praluent?
Praluent is FDA approved for the treatment of heterozygous familial hypercholesterolemia (HeFH) in combination with diet and maximum statin therapy. Another group of patients that may be considered for treatment with Praluent are patients with clinical atherosclerotic cardiovascular disease who need LDL cholesterol lowering. These patients have narrow and hardened arteries from excess cholesterol in the blood. Praluent can lower the amount of LDL in the blood and may be help stop progression of plaque formation.
HeFH is caused by family genetics and causes abnormally high amounts of LDL cholesterol. This disorder affects about 1 in 500 people. Certain subpopulations of people have a higher rate of the disorder including Christian Lebanese, Dutch South Afrikaner and people of Quebec. People with HeFH often have trouble lowering their cholesterol with diet, exercise, and statin drug therapy. Elevated LDL cholesterol is linked to heart disease and causes about 610,000 deaths in the United States (one in every four) each year.
How effective is Praluent?
In five placebo-controlled trials that included 3,499 patients 36% were patients with HeFH and 54% were patients with clinical atherosclerotic cardiovascular disease. All patients were receiving maximally tolerated doses of statins. All trials were at least 52 weeks in duration with primary endpoint (mean percent change in LDL) measured at week 24. Three studies used an initial dose of 75 mg every 2 weeks followed by up-titration to 150 mg every 2 weeks for patients who did not reach LDL goal at week 12. Most patients (57% to 83%) did not require up-titration. Two studies used a dose of 150 mg every 2 weeks.
Study 1 was a multicenter, double-blind, placebo-controlled trial with 1553 patients taking Praluent 150 mg every 2 weeks and 788 patients taking a placebo. Overall, 69% of patients were non-HeFH patients and 18% had HeFH. The difference in LDL percent change at week 24 between Praluent and placebo was -58%.
Studies 3 and 4 were multicenter, double-blind, placebo-controlled trials with 490 patients taking Praluent 75 mg every 2 weeks (42% of patients in the Praluent group were up-titrated to 150 mg every 2 weeks at week 12) and 245 patients taking placebo. All patients had HeFH. At week 12 the difference in LDL percent change compared to placebo was -48%. At week 24 the difference was -54%.
The effect of Praluent on cardiovascular morbidity and mortality has not yet been determined.
Interesting facts about Praluent
Praluent is the first PCSK9 inhibitor approved in the US.
Praluent can reduce low-density lipoprotein (LDL) cholesterol in patients already on maximum strength statin therapy.
Injections only need to be administered once every two weeks to see results.
Age, body weight, race, gender, and creatinine clearance do not significantly alter the pharmacokinetics and efficacy of Praluent – no dose adjustments are recommended.
Patients may develop antibodies against Praluent which can lead to more injection site reactions.