Merck's Big Gamble
Arcoxia probably won't get FDA approval.
By Tom Branna
Editorial Director
Fool me once, shame on you. Fool me twice, shame on me. The adage certainly fits the mood at FDA these days as Merck tries to get regulatory approval for Arcoxia, the successor to its notorious Vioxx painkiller.
In fact, one leading cardiologist recently told the press that Arcoxia won't win regulatory approval next week because studies suggest it raises the risk of heart attacks. "The studies that have been conducted do not support the approval," said Dr. Steven Nissen, head of cardiology at the Cleveland Clinic.
If Dr. Nissen is right, the rejection of Arcoxia would kill Merck’s plan of recapturing some of the $2.5 billion in annual sales that it lost when Vioxx was withdrawn from the market in 2004. Analysts had predicted that Arcoxia’s annual sales could top $1 billion.
Since Vioxx was withdrawn from the markets, consumers have filed thousands of lawsuits against the Whitehouse, NJ-based drug maker. At press time, juries had found in favor of Merck 10 times and in favor of plaintiffs five times. There are two unresolved mistrials as a result of hung juries after plaintiffs failed to prove their claims. In addition, another 14 cases scheduled for trial were either dismissed or withdrawn from the trial calendar by plaintiffs before a jury could be selected.
In a 34,000-person study, Merck said Arcoxia had the same risk on the heart and caused 30 percent fewer ulcers in the digestive tract than a decades-old arthritis drug sold in the U.S. called diclofenac. The two drugs worked the same way at reducing pain.
Yet, Dr. Nissen insists that Merck picked the wrong painkiller as its benchmark.
“They chose as a competitor the drug diclofenac, which has a worse risk of adverse cardiovascular events than Vioxx, so proving that Arcoxia is not worse than diclofenac does not reassure anybody,” Dr. Nissen told The Record, Hackensack, NJ. “They chose that comparator was because they thought it was an agent they just couldn’t lose to.”
Arcoxia, diclofenac, Vioxx and Pfizer’s Celebrex, are all non-steroidal anti-inflammatory drugs (NSAID) that block Cox-1 and Cox-2 enzymes. Arcoxia, Vioxx and Celebrex are unique because they block the Cox-2 enzyme without blocking Cox-1, which is believed to help protect the stomach.
In its defense, a Merck executive said the company chose to study Arcoxia against diclofenac because it is the most commonly prescribed NSAID in the world, though not in the U.S. Sean Curtis, Merck’s executive director for clinical research also noted that it doesn’t interfere with aspirin’s heart benefit.
Losing Sleep Over Gaboxadol
The grim outlook for Arcoxia comes less than a week after Merck said it was pulling the plug on an insomnia treatment. Late last month, Merck, along with its partner, Danish drug maker H. Lundbeck AS, said they were ending work on a new type of sleeping pill because data from recent clinical trials did not support further development.
The companies said they would no longer develop gaboxadol, which recently completed a late-stage clinical trial, and would not file for regulatory approval for the drug. Ongoing clinical studies on gaboxadol were halted.
Merck reported in October that it would delay plans to file a drug application for gaboxadol with the Food and Drug Administration until mid-2007 because of slower-than-expected enrollment of patients in clinical trials.
Janumet Gets Approval
But it’s not all bad news for Merck. On April 2, the FDA approved its latest diabetes offering Janumet, a combination drug that consists of Merck's Januvia and an older diabetes medication known as metformin. Merck said that the FDA had green-lighted Janumet for type 2 diabetes, the most prevalent form of the disease. Janumet contains metformin, a widely-prescribed diabetes drug also is sold under the brand names Glucophage, Fortamet and Riomet.
Januvia was approved by the FDA in October 2006. The drug, which is expected to become a significant revenue driver, had fourth quarter 2006 sales of $42 million.
Janumet combines a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin and metformin for the treatment of type 2 diabetes.
Janumet has been approved, as an adjunct to diet and exercise, to improve blood sugar (glucose) control in adult patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone, or in patients already being treated with the combination of sitagliptin and metformin.
"Janumet is the latest advance in Merck's longstanding commitment to developing effective medicines for type 2 diabetes," said Adam Schechter, president, United States Human Health, Merck & Co., Inc. "With Janumet and Januvia, Merck now has a growing family of products that provides physicians with important treatment options for patients with type 2 diabetes."
