Isis hopes it has a cholesterol killer

California-based biotech says its experimental drug dramatically reduces harmful cholesterol, but FDA won't get application until '08.

By Aaron Smith, CNNMoney.com staff writer

CHICAGO (CNNMoney.com) -- The California-based biotech Isis Pharmaceuticals could have an effective cholesterol-cutting blockbuster in the works, though it's still early to know for sure.

Isis (Charts) reported Sunday, at the annual meeting of the American Heart Association, that Phase 2 studies with its experimental drug showed it dramatically cut levels of harmful cholesterol.

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One of the studies focused on use of the drug - known as "301012" - in combination with other cholesterol-cutting drugs known as statins. Another study focused on use of the drug by itself, for patients who have adverse reactions to statins.

The experimental drug appears to be most effective when used at the heaviest doses: 200 mg and 300 mg.

The stand-alone study showed that over 12 weeks, levels of low density lipoprotein (LDL) known as "bad" cholesterol dropped 42 percent with the 200 mg doses, and plunged 62 percent with the 300 mg doses, according to Isis.

Levels of triglycerides, or blood fats, dropped 46 percent with the 200 mg dose and declined 43 percent at 300mg.

The drug 301012 works by breaking down RNA, a molecule similar to DNA that produces a protein called ApoB that makes LDL and triglycerides, said Isis chief executive Dr. Stan Crooke.

In this 12-week study, 301012 as a single agent caused levels of ApoB to drop 47 percent at 200 mg doses, and plummet 61 percent at 300 mg. The drug's reduction of ApoB is apparently causing the reduction in harmful LDL and triglycerides.

Isis also conducted a five-week study combining 301012 with cholesterol-cutting drugs called statins. Some well-known statins include Merck (Charts)'s Zocor, a former blockbuster that lost patent protection in June, AstraZeneca (Charts)'s Crestor, and Pfizer (Charts)'s Lipitor, the top-selling drug in the world with $12.2 billion in 2005 sales. Vytorin, a combination of Zocor and Schering-Plough (Charts)'s Zetia, is also a leader in the cholesterol-cutting market.

In the five-week study, the 301012-statin combo resulted in a 24 percent drop to ApoB with the 200 mg dose, and a 52 percent decline with the 300 mg dose, according to Isis.

The combo caused a 30 percent drop in LDL at the 200 mg dose and a 51 percent drop at 300 mg. It also resulted in a 20 percent decline to triglycerides and a 41 percent drop at 300 mg.

At first glance, 301012 might seem to be more effective as a stand-alone drug, but that's not necessarily demonstrated by these studies. The studies involve separate time spans - five weeks versus 12 weeks - so an accurate comparison cannot be made between the two.

The drug 301012 also caused slight increases in HDL, or high density lipoprotein, otherwise known as "good" cholesterol because it is beneficial to the body, according to Isis. But these increases were not strong enough to be considered statistically significant.

"We think the market potential for this drug is enormous," said Isis founder and chief executive Dr. Stanley Crooke. He said the cholesterol-cutting results were "spectacular" and "set the stage for a major advance in lipid lowering."

The market for cholesterol-cutting drug is more than $20 billion, but it will be years before the Carlsbad-based Isis can get its drug on the market, even if late-stage tests prove to be a success.

Crooke said his company plans to begin Phase 3, or late-stage trials, on the drug next year. Phase 3 studies are required before a drug can be submitted to the Food and Drug Administration for regulatory review.

Assuming further tests are successful, Crooke plans to file 301012 to the FDA in 2008 for the treatment of patients with a genetic disease that causes high levels of LDL, often resulting in heart attacks at an early age. After that, Cooke plans to file the drug for a more general treatment of high cholesterol, which could open it up to greater sales potential.

Isis is a relatively small company, with a market capitalization of less than $800 million. Over the last 12 months, the company's stock price has doubled. Isis has a drug on the market called Vitravene, a treatment for HIV-related vision problems, which is licensed by the Swiss drug giant Novartis (Charts).

Isis uses a similar type of technology as Sirna Therapeutics, a biotech that Merck bought for $1.1 billion on Oct. 31. Crooke, when asked if his company might be Merck's next take-over target, answered, "I think everybody is a potential takeover target."

Also, Crooke said he legally controls the use of RNA technology through patents, and that this could lead to a conflict with Sirna and Merck.

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Market indexes are shown in real time, except for the DJIA, which is delayed by two minutes. All times are ET. Disclaimer Morningstar: © 2014 Morningstar, Inc. All Rights Reserved. Disclaimer The Dow Jones IndexesSM are proprietary to and distributed by Dow Jones & Company, Inc. and have been licensed for use. All content of the Dow Jones IndexesSM © 2014 is proprietary to Dow Jones & Company, Inc. Chicago Mercantile Association. The market data is the property of Chicago Mercantile Exchange Inc. and its licensors. All rights reserved. FactSet Research Systems Inc. 2014. All rights reserved. Most stock quote data provided by BATS.