UPDATE 2-Isis drug meets all study goals; filing delayed

* Isis cholesterol drug meets all goals of pivotal trial

* Mipomersen cut LDL by 25 pct vs 3 pct for placebo

* Says plan to file for US, EU approval by mid-2011

* Previous expectation had been 2010 filing

* Isis shares down 14.7 percent; Genzyme up 2.1 percent (Adds share move, analyst comments, liver enzyme details)

By Bill Berkrot and Ransdell Pierson

ORLANDO, Fla., Nov 17 (Reuters) - Isis Pharmaceuticals Inc (ISIS.O) and Genzyme Corp's GENZ.O experimental drug for patients genetically disposed to extremely high cholesterol significantly lowered it in a pivotal late-stage study, according to data presented on Tuesday.

But Isis shares plunged nearly 15 percent after the company said it planned to seek approval for the drug nearly a year later than previously expected, analysts said.

The drug, mipomersen, attained the main goal of the trial, cutting "bad" LDL cholesterol by 25 percent, compared with just a 3 percent reduction from placebo in patients with a very rare condition known as homozygous familial hypercholesterolemia.

Genzyme, which will market the drug under a deal with Isis, said it expects to apply for U.S. and European approval by mid-2011.

"They pushed back the filing time frame. It had been the second half of 2010," said Leerink Swann analyst Joseph Schwartz. He said there may also be some investor concern about elevated liver enzymes seen in some patients.

People with the condition, which is inherited from both parents, tend to have cholesterol at four times normal levels and are at extremely high risk of heart attack and early death.

Mipomersen also succeeded in all the secondary and tertiary goals of the trial by cutting levels of other dangerous particles, suggesting the drug may offer benefits to patients beyond LDL reduction, researchers said

"We were very impressed," Frederick Raal, the study's lead investigator, who presented the data at the American Heart Association scientific meeting in Orlando, said in an interview.

Although the average LDL reduction with mipomersen was 25 percent, some patients achieved a "very impressive" 70 percent or 80 percent reduction, Raal said.

All but one of the 51 patients in the 26-week study were already taking maximum doses of cholesterol-lowering statins, and 74 percent were also on another cholesterol medicine, such as Merck and Co's (MRK.N) Zetia.

The trial was designed to judge the added benefit of mipomersen, given by injection once a week, on top of other medicines in patients whose average LDL was greater than 400.

Current guidelines call for LDL levels of about 100, and new guidelines are expected to call for heart disease patients to reduce LDL to about 70, said Raal, director of carbohydrate and lipid metabolism research at the University of the Witwatersrand in South Africa.

There is also a Phase III study of the drug in heterozygous familial hypercholesterolemia, in which the same tendency toward very high LDL is inherited from just one parent. It is also being studied in patients with traditional very high cholesterol.

"If it works in this condition, which is a very difficult condition to treat, it's going to work a hell of a lot better in patients with regular (high cholesterol)," Raal said.

Prior to the advent of statins, Raal said, patients with the rare homozygous condition rarely lived beyond the age of 20, and even now many need a blood filtering process similar to dialysis to remove excess LDL.

"The hope with this drug is that the addition will allow a bigger percentage to get to the levels we need to get them to, without the need for aphoresis (blood filtering)," Raal said.

Some 12 percent of patients treated with mipomersen had elevations of liver enzymes -- a marker for potential liver damage. Three patients reached between five and eight times the upper level of normal. But none had changes in other tests to indicate liver dysfunction, the companies said.

Raal said the elevated liver enzymes should not raise big safety concerns for very-high-risk patients, given the clear potential benefits of the drug. But he said this could be a concern for patients at lower risk.

"I think the data looks encouraging for this (very-high-risk) population," said Summer Street Research analyst Carol Werther. "These are patients who need this. They have a death sentence."

Isis shares were down $1.97, or 14.7 percent, at $11.43 in morning trading on Nasdaq. Genzyme shares were up 2.1 percent to $50.54. (Reporting by Bill Berkrot and Ransdell Pierson, editing by Lisa Von Ahn and John Wallace)