Portola Pharmaceuticals Inc.'s shares (NASDAQ:PTLA) rose 16 percent higher Wednesday, climbing $4.04 to close at $29.32, after the company shared top-line data from the first of two planned phase III studies showing that andexanet alfa, its universal factor Xa inhibitor antidote, met its primary and secondary endpoints. An intravenous bolus of the antidote immediately and significantly reversed the anticoagulation activity of Eliquis (apixaban, Bristol-Myers Squibb Co. and Pfizer Inc.), the company said, advancing Portola further toward its goal of filing a biologics license application (BLA) seeking accelerated approval by the end of 2015. (See BioWorld Today, March 20, 2014.)

The therapy, which would be used by patients who suffer a major bleeding event or those requiring emergency surgery, "hit the ball out of the park," Cowen and Co. LLC ananlyst Phil Nadeau told investors. Cowen projects andexanet alfa will launch in 2016, achieving $355 million in worldwide revenue in 2020 and enjoying a long commercial life well beyond the 2031 expiration of patents protecting the biologic. It has an FDA breakthrough designation and is also slated for accelerated approval.

The study, the first in a pair of two randomized, double-blind, placebo-controlled phase III trials called ANNEXA-A, was designed to evaluate the safety and efficacy of andexanet alfa in reversing Eliquis-induced anticoagulation in older healthy volunteers. In all, 33 older healthy volunteers were given Eliquis 5 mg twice daily for four days and then randomized in a 3-to-1 ratio to andexanet alfa administered as a 400-mg I.V. bolus or to placebo.

Detailed results of the trial will be presented at the American Heart Association 2014 Scientific Sessions in Chicago on Nov. 17.

In the second ANNEXA-A study, 32 healthy volunteers will get the same dose of Eliquis, then be randomized 3-to-1 to andexanet alfa administered as a 400-mg I.V. bolus followed by a continuous infusion of 4 mg/min for 120 minutes or to placebo. Portola expects to share data from that study in early 2015.

Portola is tracking efficacy in the studies by using biomarker endpoints, including anti-factor Xa levels as the primary endpoint in the study, a strategy it believes may increase the likelihood of achieving clinical, regulatory and commercial goals. Secondary endpoints include levels of plasma unbound (free fraction) of Eliquis and thrombin generation.

"Factor Xa inhibitors have demonstrated a safety advantage compared with older anticoagulants, but the number of patients on these newer drugs who are admitted to the hospital with a major bleed is growing due to their widespread adoption," said Portola CEO Bill Lis. "To address this critical need, our goal is to advance andexanet alfa to the market as quickly as possible under the FDA breakthrough therapy designation."

Portola expects to report additional data this year and next testing andexanet alfa with other factor Xa inhibitors, including its wholly owned betrixaban, an oral, once-daily therapy now in phase III testing; Xarelto (rivaroxaban, Bayer Healthcare and Janssen Research & Development LLC); Lixiana (edoxaban, Daiichi Sankyo Co. Ltd.); and Lovenox (enoxaparin, Sanofi SA). (See BioWorld Today, April 15, 2014.)

The ANNEXA-E study is expected to begin in 2015. Those studies are designed to support the company's BLA filing for accelerated approval. As part of the accelerated approval process, a phase IV confirmatory patient study evaluating outcomes with andexanet alfa is planned.

Results from three separate phase II proof-of-concept studies with Eliquis, Xarelto and enoxaparin, a low-molecular-weight heparin and indirect factor Xa inhibitor, in healthy volunteers demonstrated that andexanet alfa immediately reversed the anticoagulation activity of each factor Xa inhibitor and that the reversal could be sustained. Andexanet alfa has been shown to be well tolerated in phase I and II studies, with no thrombotic events or antibodies to factor Xa or factor X observed.