Merck's Good-Cholesterol Battle [This protagonist of this rambling write-up is Cordaptive (a.k.a. MK-0524), a combination of niacin and an anti-flushing agent derived from a failed asthma drug.] http://www.forbes.com/2007/08/29/merck-cordaptive-cholesterol-biz-sci-cx_mh_0830merck.html
by Matthew Herper
An experimental Merck cholesterol treatment could further boost the drug giant's resurgence and pose a threat to Abbott Laboratories, which last year acquired a rival for $3.7 billion to grow its own franchise of cholesterol drugs.
Merck's drug, called Cordaptive, is symbolic of the increasing stature of the company's labs. Efforts to develop it were kick-started by research chief Peter Kim shortly after he took over in 2003. Merck spent years languishing as it dealt with the fallout from its recall of the painkiller Vioxx (it still faces thousands of lawsuits). But lately it has been on a winning streak. Gardasil, its vaccine against the virus that causes cervical cancer, should generate more than $1 billion this year. Januvia, a diabetes pill, is also headed into blockbuster territory. By all rights, Cordaptive should be next.
But some doctors say they are cautious about the new Merck pill, which was recently named Cordaptive but is better known by the code name MK-0524. Data to be presented Sunday at a medical conference in Vienna show that Cordaptive cuts bad cholesterol, the stuff that sticks to arteries, by 21% and boosts the artery-cleansing good cholesterol (HDL)
, according to several Wall Street analysts. Merck says the Food and Drug Administration could approve Cordaptive in a year. Skeptics worry that the drug's effects on cholesterol might not translate into preventing heart attacks, strokes and deaths.
"A cautious skepticism is a reasonable thing," argues Allen J. Taylor, chief of cardiology at Walter Reed Army Medical Center, who has consulted for Merck but gets substantial research funding from Abbott. "You're dealing with a drug with unknown effects." Says Steven Nissen, head of cardiology at the Cleveland Clinic: "I will be looking for a very clear signal that the drug combination is safe." Nissen works with many of Merck's rivals, but not Merck
; he gives his speaking and consulting fees to charity.
Both the financial upside from Cordaptive and the doubts about whether it will work are enhanced by the failure last year of Pfizer's Torcetrapib, a drug to boost good cholesterol that was touted as potentially the biggest drug ever but ended up hurting patients. A recent article in the Journal of the American Medical Association concluded that the evidence supporting the development of such medicines was only "modest." But Pfizer's failure also means that Merck and Abbott will have the market for good-cholesterol-raisers to themselves. Cordaptive's effects on cholesterol come from niacin, a B-vitamin that has been used to treat heart patients for four decades.
Niacin should be a wonder drug. It is the only medicine that increases HDL (short for high density lipoprotein), cuts LDL (low density lipoprotein) and also reduces the amount of fat in the blood. But only a quarter of patients take it when prescribed
, says Sanjay Kaul of Cedars-Sinai Medical Center, because of an annoying but relatively harmless side effect: Niacin makes people turn beet red and feel unpleasantly hot
. Merck researchers in Canada realized that a failed asthma drug could reduce this flushing side effect in 2003.
Peter Kim, who had just taken the helm of Merck's research labs, rushed the drug into development. It represented a fast approach to entering the HDL market and an example of getting researchers in different disease disciplines to work together, a triumph for Kim as he tried to revitalize Merck's research efforts.
Next week, the FDA will hold an advisory panel on a new Merck medicine for HIV. Over the past 12 months, Merck shares have outperformed rivals like GlaxoSmithKline, Pfizer and AstraZeneca by more than 30%. Deutsche Bank's Barbara Ryan has estimated that in three years, Cordaptive could be generating $775 million in sales annually.
Abbott entered the market for niacin drugs in a big way in November when it bought smaller rival Kos Pharmaceuticals for $3.7 billion. Kos was founded by veteran drug executive Michael Jaharis in 1988 to sell a delayed-release niacin that would cause less flushing than earlier versions. That drug, Niaspan, took over the Niacin market and made Jaharis a billionaire even before he sold to Abbott. Now Abbott hopes a new version of Niaspan that is supposed to cause even less flushing will juice its growth
. But in a note to investors yesterday, Larry Biegelsen at Wachovia Securities wrote that he expects Cordaptive to take more than 50% of the niacin market, slowing Abbott's growth. Doubts about whether Cordaptive has unknown side effects--or somehow dulls the effectiveness of niacin--are the main threat to its success. Both Steve Nissen and Allen Taylor say little is known about the long-term effects of its flushing-blocker, which works by blocking a cell receptor called prostaglandin D2
. "What are the hazards of blocking a prostaglandin?" says Nissen. "We don't know."
Taylor, who conducted some of the biggest studies of Niaspan, points out that drugs like Vioxx and Celebrex worked on the prostaglandin receptor
; they ended up increasing the risk of heart attacks. He says he is worried that although Merck is conducting a big 20,000-patient study of Cordaptive, it is comparing the drug to placebo, not niacin
. Any potential effects of the prostaglandin drug might not show up. Results of that study are not expected for years.