New Cholesterol Drugs Face Doctors Seeking Heart Results

A new class of cholesterol-lowering medicines from Pfizer Inc. and Amgen Inc. may struggle to meet sales projections, as latest treatment guidelines suggest doctors should prescribe only drugs proven to help the heart.

Called PCSK9 inhibitors, the experimental drugs have drawn the interest of doctors and investors as the first treatments designed to cut LDL cholesterol, a risk for heart attack and stroke, by targeting a key gene. Studies have shown the medicines can slash LDL by half, and analysts have projected annual sales of $2 billion for the medicines by 2018.

Though U.S. regulators say they can approve the drugs based on that cholesterol-fighting power, new treatment guidelines may steer doctors away from the therapies until they are vetted in large trials testing for outcomes such as preventing heart attack, death and stroke. Amgen, one of the companies farthest along in development with its PCSK9 inhibitor, will release one-year data at the meeting of the American Heart Association that begins tomorrow in Dallas.

“The days of being able to do short-term studies showing you changed lab results and getting a blockbuster drug are over,” said Harlan Krumholz, a cardiologist at Yale University in New Haven, Connecticut. “We have too much proof that you can’t depend on them. For the general population, these drugs shouldn’t be approved until they are proven to lower risk.”

The new cholesterol guidelines from the American College of Cardiology and the heart association were released Nov. 12. They recommend only statin drugs such as Pfizer’s Lipitor and AstraZeneca Plc’s Crestor because studies involving more than 190,000 patients conclusively prove their benefit. Rivals that work differently, including Merck & Co.’s Zetia and Vytorin, haven’t been shown to reduce the risk of heart complications and weren’t backed by the doctors’ groups for routine use.

PCSK9 Developers

Roche Holding AG, Merck, Alnylam Pharmaceuticals Inc. and Eli Lilly & Co., and Sanofi and Regeneron Pharmaceuticals Inc. have PCSK9 inhibitors under development, vying for a piece of the cholesterol market valued at $34 billion, according to IMS Health Inc., a research firm.

Though some doctors insist on a stricter approach, the U.S. Food and Drug Administration will review the drugs for their overall safety and ability to improve a variety of measures, including bad cholesterol, blood pressure and inflammation, said Eric Colman, deputy director of the division of metabolism and endocrinology products. And while the approach will speed the arrival of the medicines to the market, they won’t lessen the need for outcomes trials, which can involve more than 20,000 patients and cost in excess of $500 million, to persuade doctors to prescribe the drugs.

Statin Intolerant

The medicines are being developed for people who can’t tolerate statins or who don’t get their cholesterol under control with older medicines, a group that encompasses about 12 million in the U.S. There were over 249 million prescriptions written for statins and cholesterol-lowering drugs in the U.S. last year, according to IMS Health.

Still, the broader results will be needed before the drugs are widely used, even if they are approved first for a limited number of patients, top researchers said. Mark Schoenebaum, an analyst with International Strategy & Investment Group LLC, said use of the drugs may be slow until the outcomes results are available in late 2017 or early 2018.

“These are very novel agents, they’re very exciting agents,” said Paul Ridker, a lead investigator of Pfizer’s trial and director of the Center for Cardiovascular Disease Prevention at Brigham & Women’s Hospital. “But they’re also injectable drugs, monoclonal antibodies, and they’re likely to be expensive.”

Unknown Effects

“We don’t have any data about long-term side effects or event rates,” Ridker, a professor at Harvard Medical School, said in a telephone interview. “I think we’d want those kind of data even if the FDA allowed use.”

As monoclonal antibodies, PCSK9 inhibitors are proteins grown in living cells that are injected into the body to target an enzyme produced by the PCSK9 gene. The enzyme prevents liver cells from processing LDL and clearing it from the body.

Regeneron and Amgen have said they’ll have final-stage results next year showing whether the drugs reduce cholesterol to levels beyond what patients can achieve on statins. Pfizer’s cholesterol-lowering trial, meanwhile, won’t have results until 2015 or 2016, said Tony Butler, an analyst with Barclays Plc, in an Oct. 29 investment note. The competing cardiovascular outcomes trials are slated to finish around the same time, two to three years later.

Even as the FDA says it’s sticking with the traditional approach to approving cholesterol medications, eyes will be on the results of a trial called Improve-It with Merck’s Vytorin. If the drug’s cholesterol lowering ability fails to translate into longer life and fewer heart attacks, those findings will have the potential to change the equation for the new PCSK9 drugs, the FDA’s Colman said.

“It’s not like there will be a stampede to these drugs,” said Ira Loss, an analyst at Washington Analysis who tracks the FDA. “It will be for doctors whose patients haven’t succeeded on statins, or drugs like Zetia or Vytorin.”

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