Source: Johnson & Johnson

It may seem a bit odd that drug giants Johnson & Johnson (NYSE:JNJ), Bristol-Myers Squibb (NYSE:BMY), and Pfizer (NYSE:PFE) are rooting so strongly for Portola Pharmaceuticals (NASDAQ:PTLA) to succeed.

Typically, these drugmakers either acquire small companies or attempt to outmaneuver them. But once you learn more about Portola's game-changing anticoagulant reversal drug and the billion-dollar impact it could have on demand for factor Xa drugs made by these companies, it becomes crystal clear why they're cheering Portola on.

New generation treatment
Warfarin has been a go-to therapy for doctors trying to prevent blood clots from forming in patients following surgery or suffering from heart disease for 50 years, but that's finally changing thanks to a new crop of drugs from Johnson & Johnson, Bristol-Myers, and Pfizer.

This new class of drugs works differently than warfarin. Instead of targeting vitamin K's ability to clot blood in the body, Johnson's Xarelto and Bristol-Myers and Pfizer's Eliquis reduce the production of Factor Xa, an enzyme that contributes to thrombin production, a key cog in blood coagulation.

Thanks to the potential for factor Xa drugs to reduce the risk of brain hemorrhage and avoid constant monitoring and drug-dosing adjustments, doctors are increasingly embracing them instead of warfarin and that's helping Johnson, Bristol, and Pfizer's sales head higher. But the drugs still have one big problem: There isn't an antidote.

That's a big disadvantage versus warfarin. If patients suffer a bleeding event when taking it, doctors simply prescribe vitamin k to reverse its effects. But if a factor Xa patient shows up in the emergency room bleeding, their options are far more limited. As a result, many doctors are hesitant to prescribe Xarelto and Eliquis and others avoid them altogether for use in older patients who are more at risk of bleeding.

Hundreds of millions of reasons
Despite lacking an antidote, the factor Xa drugmakers have a significant revenue opportunity given that as many as 40%-60% of the 800,000 patients undergoing orthopedic surgery may develop blood clots and that cases of atrial fibrillation, a condition for which warfarin is commonly prescribed, is on the rise.

Johnson, which markets Xarelto in the U.S., has seen its sales of the drug climb steadily from $270 million in the fourth quarter, to $319 million in the first quarter, and $361 million in the second quarter. Johnson's partner, Bayer, which markets Xarelto overseas, sold $910 million worth of Xarelto in the first half of 2014, too.

Source: Bristol-Myers Squibb

Sales of Bristol and Pfizer's Eliquis are smaller, but are growing quickly. Eliquis revenue jumped from $22 million in the first quarter of 2013 to $106 million in the first quarter of 2014, to $171 million globally in the second quarter.

So, while Johnson, Bristol, and Pfizer already realize hundreds of millions in sales from their factor Xa drugs every quarter, sales could go even higher if an antidote makes its way past regulators and clears the way for their use in more patients.

Stepping into the void
In a bid to accelerate the approval of such an antidote, Johnson is helping pay for Portola's clinical trials of andexanet alfa, a drug that works by acting as a decoy that factor Xa drugs target instead of the enzyme. In phase 2 trials, Portola's andexanet alfa successfully reversed Xarelto's effects, prompting the FDA to grant the drug breakthrough designation and the company to launch phase 3 trials. 

Bristol-Myers and Pfizer are financing Portola studies that are evaluating andexanet alfa's ability to reverse Eliquis, too. This week, Portola reported that its first small phase 3 trial was a success and while Portola will present more detailed information from the study at an industry conference in the middle of November, the headline is that the drug worked well enough that Portola plans to file for FDA approval next year.

And another thing
The ability to expand the patient pool for Johnson & Johnson, Bristol-Myers, and Pfizer is compelling, but it's also intriguing to learn that despite the collaboration with Portola by these companies, Portola retained full commercial rights to the drug. Even more interesting is that Portola is not only working on an antidote, but developing its own factor Xa drug that could someday compete with Xarelto and Eliquis.

Portola's trial results appear solid, but it's still a development stage company without any commercial products. That suggests that less risk tolerant investors would likely be better served focusing on Portola's potential to help Johnson, Bristol-Myers, and Pfizer's sales grow. But for speculative investors willing to take on some risk, buying Portola may make sense.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.