Merck's niacin combination product is moving into a 20,000-patient, $79.2 mil. clinical trial.

The firm has granted Oxford University's Clinical Trial Service Unit £42 mil. to conduct a second Heart Protection Study. HPS2-THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) will evaluate the combination treatment's impact on heart attack and stroke prevention by increasing HDL cholesterol.

The university announced May 31 that it would begin recruiting 20,000 patients into the trial later this year.

The major international trial will evaluate MK-0524A, a fixed-dose combination of extended-release niacin and prostaglandin D2 blocker MK-0524, which minimizes flushing associated with niacin. The aim of the trial is to see if the combination, by increasing HDL cholesterol, can further drive down the risk of heart attack and stroke among patients taking treatment to lower LDL cholesterol.

"This new treatment should produce an average increase in HDL cholesterol of around 20%, which might realistically translate into a reduction of about one-fifth in the risk of suffering a heart attack or stroke or of being killed by vascular disease," the Oxford University researchers said.

In December, Merck said it expected to file NDAs for MK-0524A and a second investigational combination, MK-0524B (which adds Zocor (simvastatin) to the combination), in 2007 without conducting major outcomes studies, due to the availability of data on niacin (¹ Also see "Merck Unveils HDL-Cholesterol Drug Candidates" - Pink Sheet, 15 December, 2005.).

Nonetheless, Merck said at that point that it was committed to demonstrating proven outcomes of its drugs.

The firm reported problems with the formulation of MK-0524B in March, but maintained that the timeline for filing has not changed (² Also see "Merck’s HDL-Raising Cholesterol Combo Has “Formulation Issues”" - Pink Sheet, 8 March, 2006.).

Niacin has been shown to be an effective HDL-raising agent, but the drug is difficult to take long-term because of the flushing side effect, which is caused by dilating blood vessels in the skin through the release of prostaglandin D2.

Early studies of daily doses of the niacin/MK-0524A combination have shown that it substantially increases HDL cholesterol with a lower frequency and intensity of flushing, the researchers noted.

Despite Merck's funding, CTSU said it designed the study and will analyze the results independently.

The trial will recruit men and women ages 50 to 80 years with a history of heart attack, stroke or peripheral arterial disease. Up to 7,000 patients will also have diabetes. The Oxford CTSU will be the central coordinating center with three regional centers in the U.K., China and Scandinavia.

Patients will first be treated with statin therapy to lower LDL cholesterol. They will then be randomly assigned to receive the new combination drug or placebo daily for four years. Participants will be evaluated at three and six months and every six months thereafter.

Lead investigator Jane Armitage called the study "a natural follow-up to our Heart Protection Study of LDL-lowering therapy."

The results of the initial Heart Protection Study led to an amended label for Merck's Zocor. That five-year study showed a 38% reduction in non-fatal heart attacks and a 25% reduction in the risk of stroke in at risk patients treated with Zocor.

- Jessica Merrill

Merck’s Niacin Combination Drug To Be Evaluated In Heart Protection Study 2

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