| NEW YORK
NEW YORK Bristol-Myers Squibb Co and Pfizer Inc could provide new data within days on an experimental blood thinner, revealing its potential in a highly lucrative market for millions of patients with dangerously irregular heart rhythms.
Their pill, apixaban, if approved, will likely be the third entrant among a new crop of oral anti-coagulants meant to replace warfarin, the current standard for preventing stroke among patients with atrial fibrillation. Each of the medicines has the potential for topping $2 billion in annual sales.
Even if late to market, apixaban could catch up with rival newcomers thanks to Bristol-Myers' and Pfizer's vast sales networks for cardiovascular treatments -- but only if data from the highly-awaited Phase III trial measure up.
"Because this is the third entrant in, the data need to be pretty good," said Sanford Bernstein analyst Timothy Anderson.
The other two are Boehringer Ingelheim's Pradaxa, or dabigatran, which is already on the market, and Xarelto, or rivaroxaban, a drug developed by Bayer AG and Johnson & Johnson that is awaiting U.S. approval.
But Pfizer and Bristol are uniquely placed to make up that lost ground due to the relationships they have built with doctors in selling their respective cholesterol fighter Lipitor and blood clot preventer Plavix -- the world's two biggest selling medicines.
"Pfizer and Bristol both have so much more cardiovascular marketing muscle compared with Boehringer Ingelheim or J&J or Bayer," Bernstein's Anderson said. "When you're the third product in, but you're being sold by the two big cardiovascular gorillas ... it's a lot easier to go into (doctors') offices."
Wall Street expects the new drugs and a likely fourth entry from Daiichi Sankyo Co Ltd called edoxaban, collectively to fetch more than $10 billion a year. Atrial fibrillation will account for the lion's share of revenue, but they will also be used to prevent blood clots in patients undergoing hip and knee replacements.
Many investors expect Bristol-Myers and Pfizer to unveil by month's end general findings from their study, called ARISTOTLE, with full results to be presented in late August.
The Phase III apixaban data could give Bristol-Myers stock a nice bump or send it reeling, JP Morgan analyst Chris Schott said.
"Despite relatively high expectations reflected for the product already, any comment about a statistically significant improvement in efficacy or bleeding would be a positive catalyst for the stocks," Schott said in a research note, suggesting shares could rise 5 percent.
"In the very unlikely event the study misses its primary endpoint, we would anticipate Bristol-Myers shares could be down 10 percent," Schott added.
A LOW THRESHOLD
Warfarin has been used for more than half a century, but carries serious bleeding risk, requires frequent dose adjustments and imposes strict dietary restrictions.
The bar for the apixaban trial's success is therefore not especially high, as the drug needs only to show it is as effective, or non-inferior, to warfarin to meet the main goal.
Investors will also be looking for clues as to how it might stack up against Pradaxa and Xarelto.
"If apixaban had much better efficacy than warfarin and also statistically significantly less bleeding, that would be the home run data, but to me that doesn't seem very likely," Anderson said. "The other two products had one or the other.
"All of these are going to have some good element and some not so good element and they are going to end up being fairly comparable in the eyes of prescribers," Anderson added.
Pradaxa reduced stroke risk 35 percent at its higher dose compared with warfarin in a pivotal Phase III trial, while Xarelto reduced risk 21 percent in its Phase III and greatly reduced risk for more serious hemorrhagic strokes.
Leon Henderson-MacLennan, medical consultant with the inThought unit of Wolters Kluwer, said the apixaban stroke reduction rate could be lower than its rivals, but show a lower bleeding risk and still be seen as a success.
"We're looking for a nice, safe way of reducing risk and, if we can see that in a statistically significant fashion, even if the relative risk reduction was 15 percent, that would still indicate it will be an option on the market," he said.
"The devil is going to be in the details in terms of how we choose one versus another. Right now they all look like viable options and I don't see one clearly outshining the other," Henderson-MacLennan said.
Pfizer and Bristol both need new products to make up for the imminent U.S. patent expirations and steep sales declines of Lipitor and Plavix.
Apixaban will clearly have some hurdles to overcome, namely Pradaxa's healthy head start in the market and Xarelto's more convenient once-daily dosing. The Bristol drug and Xarelto are taken twice a day by atrial fibrillation patients.
Jack Lawrence, Bristol's head of development for apixaban, suggested that twice daily dosing is superior as it allows for fewer peaks and valleys of the drug in the system.
Lawrence also said apixaban demonstrated good tolerability with no gastrointestinal side effects. G.I. problems have been associated with Pradaxa use.
But Dr. Larry Chinitz, director of the Heart Rhythm Center at New York University Langone Medical Center, said a once-a-day drug would be preferable.
"If the drugs appear to be equally efficacious, then patients will prefer to take it once a day," Chinitz said.
"Anything that improves compliance, especially for one that is so important as a blood thinner for stroke prevention, that would be a significant issue."
(Reporting by Ransdell Pierson and Bill Berkrot; editing by Michele Gershberg and Andre Grenon)