Biotech Values

[DewDiligence]

Niaspan Bests Zetia With Ease in ARBITER 6–HALTS Study

[This is the study sponsored by Walter Reed Army Medical Center that was stopped early because one drug was clearly superior in either safety or efficacy. As it turns out, ABT’s Niaspan was statsig superior to MRK’s Zetia on the primary (efficacy) endpoint of carotid intima-media thickness as well as the secondary (safety) endpoint of MACE. Inasmuch as MRK has been talking down the relevance of this study for the past few weeks, the outcome of the study is hardly a surprise (#msg-43443829).]

http://www.reuters.com/article/marketsNews/idCNN156345220091116

›Sun Nov 15, 2009 7:57pm EST
By Bill Berkrot and Ransdell Pierson

ORLANDO, Nov 15 (Reuters) - Abbott Laboratories' (ABT) Niaspan appeared to be more effective and safer than Merck & Co's (MRK) Zetia as a supplementary cholesterol treatment to statins, according to a small study that is likely to further tarnish Merck's damaged cholesterol franchise.

The damage, however, may be limited by the limitations of the study itself, which included data from just 208 patients and was criticized in a major medical journal.

"Niacin is the clear winner and led to very clear reductions in the amount of atherosclerosis that patients had," Alan Taylor, the study's lead investigator who will present the data on Monday at the American Heart Association scientific meeting in Orlando, Florida, said in an interview on Sunday.

Atherosclerosis, which occurs when there is a build-up of dangerous plaque in the arteries, can lead to heart attacks.

Two earlier studies had led to questions about the value and effectiveness of Zetia and a related Merck drug, Vytorin, after which sales of the medicines plunged, although it remains a $4 billion a year franchise.

"This trial doesn't quite put the nail in the coffin for ezetimibe, but it pushes it way down on the list of medications for cholesterol-lowering therapy," Anthony DeMaria, editor-in-chief of the Journal of the American College of Cardiology, said in a statement, using the chemical name for Zetia.

Jon LeCroy, an analyst with Hapoalim Securities, said the study could have a sharp negative effect on Merck's cholesterol franchise.

"This is a huge negative because the excess heart attacks raise significant concern, and front-page headlines will cause worried patients to call their doctors," LeCroy said. He speculated U.S. sales of Zetia and Vytorin could fall another 10-15 percent on the news.

The study tested the effect on carotid artery wall thickness of adding either Niaspan, a long-acting niacin that raises good HDL cholesterol, or Zetia, which lowers bad LDL levels. It involved patients who had heart disease or high risk of heart disease whose LDL was already at target levels from taking statins -- the first-line treatment for high cholesterol -- but who had low HDL levels.

Increases in thickness of the artery wall could be an indicator of build-up of dangerous plaque that causes atherosclerosis, while a decrease could indicate regression of the disease.

The 14-month, 363-subject study sought to determine whether a patient on statins in need of additional therapy would benefit more from further driving LDL down or raising HDL. "This is a question that clinicians are faced with every single day," Taylor explained.

Even though the study was halted early, with 14-month data available for only 208 patients, "Niaspan turned out to be clearly superior to ezetimibe," Taylor said.

Niaspan patients had an average reduction in carotid artery wall thickness -- known as intima-media thickness – of 0.014 millimeters compared with no real change in the Zetia group.

DIFFERENCE IN ADVERSE EVENTS

Perhaps of more concern was the five times difference in major adverse events, defined as heart attack, death from heart disease, need for artery-clearing procedures or hospitalization for acute coronary syndrome, although the numbers were small.

There were nine major adverse events in the Zetia group of patients, or 5 percent, compared with two with Niaspan, or 1 percent.

Taylor recommended that doctors refrain from using Zetia in patients until data becomes available that shows it definitively prevents heart attacks and strokes. Merck is currently conducting a large study it hopes will prove just that.

AHA spokesman and former president Robert Eckel said the independent safety monitoring board for the large Merck study "has not seen any safety signal surface." Therefore, Eckel said, "I see no reason to be concerned about using Zetia for LDL lowering."

"The American Heart Association is driven by science, and at this time there is no evidence the drug does harm," he said.

But Taylor said, "To assume that a drug is OK just because LDL goes down is no longer an assumption you can make."

A pair of editorials in the New England Journal of Medicine, however, questioned Taylor's study and its conclusions. "Unfortunately, the premature termination of the trial, the small number of patients studied and the limited duration of follow-up preclude us from conclusively declaring niacin the adjunctive agent of choice," one editorial concluded, adding that the result "does not necessarily merit changes in our lipid-lowering guidelines at this time."

A second editorial said not including data from all 363 patients was a missed opportunity to enhance the study's precision. Despite the study's "several limitations," it said "the primary results are likely to be correct, although the magnitude of the difference between the treatment arms may be overestimated."

But Merck research chief Peter Kim defended his company's drug, calling Taylor's study, "scientifically inadequate." "It would be inappropriate in my opinion for physicians to be taking (this) data and making any changes in their clinical practice with regard to these drugs. It would not be good for public health," Kim said.‹