The FDA has approved Sanofi and Regeneron Pharmaceuticals’ Praluent (alirocumab) Injection, the first FDA-approved treatment in a new class of drugs known as PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Praluent is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein (LDL) cholesterol. The effect of Praluent on cardiovascular morbidity and mortality has not been determined.

Praluent is the first and only PCSK9 inhibitor approved in the U.S. and is available in two different doses (75mg and 150mg). Both doses of Praluent are available in a single 1mL injection delivered in a single-dose prefilled pen or syringe that patients self-administer every two weeks.

“For patients with high LDL, or bad cholesterol, the primary focus of treatment is to lower their levels, but many patients today do not achieve recommended levels despite lifestyle modifications and treatment with statins,” said Christopher Cannon, M.D., professor of Medicine at Harvard Medical School, Cardiovascular Division at Brigham and Women’s Hospital, and a member of the Steering Committee for the phase III ODYSSEY clinical trial program. “In the ODYSSEY clinical trial program, two doses of alirocumab showed significant LDL cholesterol lowering in a variety of patients who were not able to adequately lower their LDL cholesterol with current standard-of-care alone. The majority of patients achieved their LDL-lowering goals with the 75mg dose, when added to maximally tolerated dose of a statin, with a generally acceptable safety profile.”

Many patients in the U.S. face the challenge of achieving LDL cholesterol levels recommended by healthcare providers, despite treatment with standard-of-care including statins. These include approximately 8-10 million patients with an inherited form of high LDL cholesterol, known as heterozygous familial hypercholesterolemia, and those with clinical ASCVD, defined as a build-up of plaque in the arteries that can lead to reduced blood flow and a number of conditions including heart attack, stroke, chest pain (stable or unstable angina), transient ischemic attack, revascularization and peripheral artery disease.

The approval of Praluent was based on data from the pivotal phase III ODYSSEY program, which showed consistent, positive results compared to placebo and included current standard-of-care therapy (statins). In the ODYSSEY LONG TERM trial, which evaluated Praluent 150mg every two weeks, Praluent reduced LDL cholesterol by 58% versus placebo at week 24 when added to current standard-of-care, including maximally tolerated statins. In ODYSSEY COMBO I, Praluent 75mg every two weeks as an adjunct to statins reduced LDL cholesterol by an additional 45% compared to placebo at week 12. At week 24 in the same trial, Praluent reduced LDL cholesterol by an additional 44% compared to placebo. In this study, if additional LDL cholesterol lowering was required based on pre-specified criteria at week eight, Praluent was up-titrated to 150mg at week 12 for the remainder of the trial. Eighty-three percent of patients remained on their initial 75mg dose.

Praluent is generally well-tolerated with an acceptable safety profile. Local injection site reactions including redness, itching, swelling, or pain/tenderness where the injection is given were the most common events (7.2% with Praluent v. 5.1% with placebo) and resulted in a low discontinuation rate that was comparable to placebo (0.2% with Praluent v. 0.4% with placebo). Patients receiving Praluent had a greater number of injection site reactions, had more reports of associated symptoms and had reactions of longer average duration than patients receiving placebo. Other common adverse events occurring more frequently in patients with Praluent than placebo included symptoms of the common cold and flu or flu-like symptoms.

The companies carefully considered the potential medical value that Praluent offers patients in determining the Wholesale Acquisition Cost (WAC). The U.S. WAC price of Praluent is $40 per day ($1,120 every 28 days) for both the 75mg and 150mg doses, making Praluent the lowest priced patient-administered monoclonal antibody therapy on an annualized basis. Actual costs to patients, payers and health systems are anticipated to be lower as WAC pricing does not reflect discounts or rebates. Out-of-pocket costs to patients will vary depending on insurance status and eligibility for patient assistance.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorization of Praluent, recommending its approval for use in certain adult patients with hypercholesterolemia. The European Commission is expected to make a final decision on the Marketing Authorization Application for Praluent in the E.U. in September.