Genzyme and Isis say mipomersen, which treats genetic cholesterol disease, succeeded in study

Genzyme, Isis say cholesterol drug met trial goal

NEW YORK — Genzyme Corp. and Isis Pharmaceuticals Inc. said Wednesday their cholesterol drug mipomersen met its goals in a study that tested the drug on patients with a genetic disorder that raises levels of “bad” cholesterol in the blood.

Despite the positive results, Isis shares plunged after the company said it wants to finish other studies and get the drug on the market before it seeks approval for the illness that was part of the trial. It plans to file first for approval in other cholesterol diseases that are less common and more severe.

In midday trading, Isis shares slid $1.55, or 14 percent, to $9.49. Earlier they set an annual low of $8.85.

After six months of treatment in the study, LDL cholesterol levels of patients injected with mipomersen fell 28 percent, the companies said. Patients given a placebo injection experienced a 5 percent rise in their cholesterol levels. The trial studied mipomersen against heterozygous familial hypercholesterolemia, one of several types of genetic high cholesterol diseases.

Mipomersen was discovered by Isis, of Carlsbad, Calif., and licensed to Genzyme, which is based in Cambridge, Mass. Genzyme shares fell 32 cents to $54.55.

Patients with familial hypercholesterolemia, or FH, have LDL cholesterol receptors that do not work well, which leads to higher LDL levels and greater risk of heart disease. Patients are said to have the heterozygous FH if they inherited a defective gene from one parent.

In 2011, the companies plan to ask the FDA and European Union regulators to approve mipomersen as a treatment for a rarer and more severe type of the disease, homozygous FH, which is inherited from both parents. They may also ask for approval in severe hypercholesterolemia.

The companies did not say when they would ask for approval in heterozygous FH, which affects about one person out of 500. About one person in a million has homozygous FH. But Isis Chairman and CEO Stanley Crooke said the company is taking a careful path toward approval in heterozygous FH and other less severe indications. He said that will increase their chances of success.

“Only after we’ve completed additional studies that enhance the safety database and we have commercial experience will we take the next step and seek approval for heterozygous FH patients in Europe,” he said. “After that, we’ll complete additional studies … before we seek any further indications.”

Later this year, the companies expect results from a study of mipomersen in patients with severe hypercholesterolemia, and a study involving patients with hypercholesterolemia with high risk for coronary heart disease.

All of the patients in the trial had coronary artery disease and were taking statin drugs to treat it, the companies said. Many of the patients were also using other cholesterol drugs. They were injected with 200 milligrams of mipomersen or the placebo once per week for six months.

Genzyme and Isis said 83 patients were given mipomersen during the study. Nine left the trial early due to side effects. The most common side effects were reactions at the site of injection, and flulike symptoms. In an earlier study, four out of 34 mipomersen patients stopped treatment due to side effects.

Patients with familial hypercholesterolemia have LDL cholesterol receptors that do not work well, but still function somewhat. In homozygous FH, the receptors do not work at all.