TRENTON - An experimental anti-clotting drug that Merck & Co. is developing was found to increase risk of dangerous internal bleeding in a second study, meaning it's unlikely to achieve the blockbuster status once expected, if it's even approved.
Vorapaxar is part of a new generation of anti-clotting drugs meant to prevent the death and disability strokes and heart attacks cause in the millions of people at risk for them. Drugmakers have generally touted their compounds as more effective and safer than Coumadin, known chemically as warfarin, the standard treatment for decades despite the need for frequent blood tests because getting the dosage right is so tricky.
On Tuesday, Merck said top-line results from a 26,000-patient study called TRA-2P show vorapaxar, when added to standard anti-clotting therapy, significantly reduced risk of heart attack, stroke, and death from heart disease or emergency heart surgery.
But the company said there was a significant increase in bleeding, including bleeding inside the skull. That can cause a stroke, brain damage or death. Such intracranial bleeding was less common in patients who had not previously had a stroke.
A year ago, the same bleeding problem led safety monitors to halt a late-stage study of vorapaxar called Tracer. That international study included nearly 13,000 patients who had had a heart attack or severe chest pain from clogged arteries.
At the time, Merck decided to continue the TRA-2P study but to no longer give vorapaxar to about 6,000 patients in that study who had a history of stroke.
"We believe commercialization is unlikely, given the potential safety profile of the drug and negative results from Tracer," Citi analyst John Boris wrote to investors. "If vorapaxar reaches the market, we see a limited commercial" opportunity.
He still has a "Hold" rating on Merck but wrote off any chance of vorapaxar sales in January 2011.
Merck basically conceded the drug's diminished prospects when it took a $1.7 billion charge a little over a year ago to write down the value assigned to vorapaxar when it acquired the compound through its November 2009 purchase of Schering-Plough Corp.
Merck, based in Whitehouse Station, N.J., and with operations in the Philadelphia region, said it will present detailed results from TRA-2P at the March 24-27 meeting of the American College of Cardiology.
"We are pleased that TRA-2P met its primary endpoint, and we look forward to discussing the results with the scientific community," Peter Kim, president of Merck Research Laboratories, said in a statement.
Merck has said it plans to apply for approval of five different drugs between this year and next. Vorapaxar is not on the list, although Merck originally had planned to apply for approval in 2011.
Meanwhile, rival drug companies have gotten new anti-clotting drugs approved recently or expect a ruling on their drug shortly. Those are: Boehringer Ingelheim of Germany, whose Pradaxa was approved in October 2010; partners Johnson & Johnson and Bayer Healthcare, whose Xarelto was approved last July, and partners Pfizer Inc. and Bristol-Myers Squibb Co. Their Eliquis is expected to get a ruling from the Food and Drug Administration by March 28.
None of those drugs has shown such serious bleeding risks, but they are far more expensive than warfarin.
In midday trading, Merck shares were up 28 cents at $38.68.
STRIKE TWO: A second study shows Merck's experimental anti-clotting drug vorapaxar increased risk of dangerous internal bleeding, including inside the skull. The study, called TRA-2P, did show vorapaxar lowered risk of heart attack, stroke and death.
DIM FUTURE: Merck's already taken a $1.7 billion charge over vorapaxar after it flopped in the earlier study. It's to release full results of the latest study in late March.
ANALYST VIEW: Citi's John Boris thinks approval is unlikely. If it happens, he writes, vorapaxar has "limited commercial" opportunity.
Linda A. Johnson can be followed at http://twitter.com/LindaJ,onPharma
Tuesday, February 07, 2012
Merck anti-clot compound again shows bleeding risk