New blood thinner antidote to help doctors move past warfarin

By Bill Berkrot

New York: A new class of blood thinners that competes with widely used warfarin should get a boost next year when an "antidote" that can reverse the medications' effects in an emergency is expected to enter the market, according to top U.S. heart doctors and investors.

Xarelto, from Bayer AG and Johnson & Johnson , and Eliquis, sold by Bristol-Myers Squibb and Pfizer, were approved as safer and more convenient alternatives for preventing blood clots and strokes than warfarin.

But there was one hitch: there was no way to quickly restore normal clotting for patients in need of emergency surgery or to stop a major bleeding episode, leading many doctors to hold off on prescribing the drugs.

"It may be uncommon, but they're memorable when they happen," Dr. Charles Pollack, an emergency physician at Thomas Jefferson University Hospital in Philadelphia, said of major bleeding events.

"We didn't have a specific reversal strategy for these drugs, and I think that left people feeling a bit insecure," added Pollack, who has done clinical work on a recently approved antidote to Boehringer Ingelheim's rival blood clot preventer Pradaxa.

That is about to change.

Small drugmaker Portola Pharmaceuticals this month applied for U.S. approval of a drug called andexanet alfa that rapidly reverses the effect of Xarelto and Eliquis. It is expected to enter the market in 2016.

"It will make a big difference," said Dr. Mariell Jessup, a cardiologist at the University of Pennsylvania Medical Center. "I have many physicians, particularly surgeons, who hate these drugs. They're frightened of them because they've had to deal with the consequences of somebody coming in with trauma," while using the new blood thinners.

The new drugs cause fewer major bleeding episodes than warfarin and do not require dietary restrictions or constant monitoring as with the decades-old medicine. But major bleeding remains the most worrisome risk of all anti-coagulant therapy as it can be fatal or cause debilitating, long-term problems.

Bristol-Myers reported $466 million in global third-quarter sales of Eliquis, which won U.S. approval at the end of 2012, about 18 months after Xarelto. J&J posted U.S. Xarelto sales of $461 million in the quarter, while Bayer reported about $509 million in international sales.

There is still a lot of room to grow as warfarin, also prescribed under the brand name Coumadin, commands some 60 percent of the blood thinner market. Morningstar expects annual sales for Xarelto and Eliquis could reach $8 billion for each.

PAYERS SEE VALUE

The treatments are about 70 times more expensive than pennies-a-day warfarin, according to Express Scripts Holding Co , the largest U.S. pharmacy benefits manager. But given the superior safety and convenience, Express Scripts said in a statement that "the overall value is likely justified."

Health insurer Aetna Inc expects approval of the Portola drug to gradually increase use of Xarelto and Eliquis, said Edmund Pezalla, Aetna's national medical director for pharmaceutical policy and strategy.

Xarelto and Eliquis are approved to treat patients with a type of irregular heartbeat called atrial fibrillation that significantly increases stroke risk, as well as to prevent blood clots following hip or knee replacement, and to treat deep vein thrombosis and pulmonary embolism.

Paul Burton, vice president of medical affairs for Johnson & Johnson's Janssen unit, stressed Xarelto's safety but said availability of Portola's drug would enhance doctor comfort levels.

The Xarelto partnership is seeking additional approved uses, with trials underway in patients with acute coronary syndrome, and for reduction of major adverse cardiovascular events in patients with heart failure or peripheral artery disease.

Bristol and Pfizer have a direct-to-consumer television ad campaign to increase Eliquis awareness.

"We believe that a reversal agent could be an important consideration for physicians when initiating Eliquis and switching appropriate patients from warfarin to Eliquis," Bristol and Pfizer said in a joint statement.

Portola's reversal drug "will certainly help sales. Anybody who was waiting on the sidelines will not be fence-sitting anymore," said Les Funtleyder, healthcare portfolio manager for E Squared Capital Management, which holds Pfizer shares.

The drug would become Portola's first product on the market.

Cowen and Co forecast $355 million in sales by 2020 for the antidote. Portola is also developing a drug to rival Xarelto and Eliquis.

Duke University's Dr. Jerrold Levy predicted that all hospitals will stock the Portola antidote.

"It increases the safety margin," Levy said.