PCSK9 inhibitor approved for lowering cholesterol

FDA has approved evolocumab (Repatha, Amgen) injection, a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), for some patients who are not able to adequately control low-density lipoprotein (LDL) cholesterol with current therapies. 

Evolocumab, which is the second drug that FDA approved in a new class of drugs known as PCSK9 inhibitors, is indicated for use as an adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease (ASCVD), who need additional lowering of LDL cholesterol. In July, Sanofi and Regeneron Pharmaceuticals received FDA approval for the first PCSK9 inhibitor-alirocumab (Praluent).

“Through PCSK9 inhibition, evolocumab substantially reduces LDL or ‘bad’ cholesterol, a well-validated, modifiable risk factor for cardiovascular disease,” said Marc Sabatine, MD, MPH, chairman of the TIMI Study Group, and professor of medicine at Harvard Medical School, Boston. “Many patients still require further LDL cholesterol lowering and evolocumab now offers an important new treatment option for them.”

According to Amgen, the manufacturer of evolocumab, there are 11 million individuals in the United States with ASCVD and/or familial hypercholesterolemia with uncontrolled levels of LDL cholesterol over 70 mg/dL, despite treatment with statin therapy or other cholesterol-lowering agents. Approximately 1 million in this country have familial hypercholesterolemia and only about one percent have been diagnosed.

Clinical results

Evolocumab was evaluated in one 52-week placebo-controlled trial and eight 12-week placebo-controlled trials in individuals with primary hyperlipidemia. In those individuals with clinical ASCVD or HeFH, evolocumab reduced LDL cholesterol by approximately 54 to 77 percent compared with placebo. In one phase 3 trial, 90 percent of patients with clinical ASCVD were able to reduce LDL cholesterol levels less than 70 mg/dL with the PCSK9 inhibitor and maximum doses of stains. In addition, patients with HoFH were able to achieve a 30 percent reduction in LDL cholesterol with evolocumab compared to the placebo group.

Evolocumab’s recommended dose for adults is a single-use 140-mg prefilled autoinjector or syringe every two weeks or 420 mg once a month. For adults with HoFH, the recommended dose is 420 mg once a month.

High-priced agent

The U.S. wholesale acquisition cost price of evolocumab is $542.31 for one single-use 140-mg prefilled dose, or $14,100 annually for the administration every two weeks. The drug’s 140-mg dose is expected to be available the first week of September, and the 420-mg once monthly dosing option is expected next year, according to Amgen.

Express Scripts, the leading pharmacy benefit manager in the United States, has reservations about the cost of the new class of cholesterol-lowering agents. At the end of July, the company warned that “PCSK9 inhibitors are on a path to become the costliest therapy class this country has ever seen.” The PBM launched its Cholesterol Care Value Program at that time to control drug utilization, ensuring that only the “right patients” will receive these new cholesterol-lowering medications.