Genetic discovery leads to additional cholesterol-lowering drugs

On June 9, 2015, the FDA’s Endrocrinologic and Metabolic Drugs Advisory Committee (EMDAC) recommended by a vote of 13 to 3 the approval of the investigational therapy Praluent™ (alirocumab injection), submitted by Sanofi-Aventis U.S. LLC and Regneron Pharmaceuticals, Inc. under biologics license application (BLA) 125559, for the long-term treatment of adult patients with high cholesterol. While the FDA is not bound by the EMDAC recommendation, it usually follows the advice of its advisory committees. On June 10, the EMDAC considered the safety and effectiveness of BLA 12552, submitted by Amgen Inc. for its Repatha (proposed trade name) (evolocumab injection), and voted 15-0 to recommend Repatha for approval.

Alirocumab

Praluent (alirocumab) is proposed to reduce bad cholesterol (LDL) and increase good cholesterol (HLD) either in combination with a statin or as monotherapy including in patients who cannot tolerate statins.

Evolumcumab

Repatha (evolumcumab) is proposed to reduce bad cholesterol and to increase good cholesterol either in combination with a statin or statin with other lipid-lowering therapies, or alone, or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate. The committee will also discuss the safety and efficacy of evolocumab in patients at least 12 years of age with genetic disorders characterized by high cholesterol.

Genetics-based discovery

According to the New York Times, both drugs were designed to mimic mutations in a gene, PCSK9, which protects people from getting heart disease. Clinical results indicate that most people who are given the drugs have had their LDL cholesterol levels drop from 40 to 65 percent.

“The discovery of PCSK9 as a powerful regulator of cholesterol levels and cardiovascular disease was one of the most important human genetic advances of the last decade,” said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President, Regeneron Laboratories. “Today’s outcome brings us one step closer to translating this genetics-based discovery into a treatment that may help the many patients in need of additional cholesterol lowering.”

The view of committee experts

The Times reports that committee experts who voted not to recommend approval wanted to wait until they had results from larger clinical trials that better established the effectiveness of alirocumab. They also were concerned that clinical trial participants would drop out of the trials once the drugs were approved so they could be sure they were getting the actual drug and not a placebo.

The Times also reports that some of the experts were only comfortable recommending approval for people with genetic disorders characterized by high cholesterol, that are unable to control their cholesterol level with statins alone. Other experts favored allowing use of the drug by the much larger group of people at high risk of heart disease for whom statins are insufficient, according to the Times.

Cost of the drugs

The Times states, according to Dr. William Shrank, chief scientific officer at CVS Health, that because the drugs are monoclonal antibodies, produced from living cells at great expense, they will cost between $7,000 to $12,000 a year. In addition, the Times reports that Shrank believes: (1) if the drugs are restricted to people with high cholesterol levels who cannot get their LDL low enough with statins, the annual cost would be $16 billion; (2) if people who are intolerant to statins are included, the annual cost would be $36 billion; and (3) if people with a history of heart disease are included, the annual cost could be $166 billion.

The EMDAC has made briefing documents for both products available to the public: