Wonder Drug Meets All Endpoints for Portola, Bristol-Myers Squibb and Pfizer
June 22, 2015
By Alex Keown, BioSpace.com Breaking News Staff
SOUTH SAN FRANCISCO – An experimental anticoagulant drug under joint development between Portola Pharmaceuticals, Inc., Bristol-Myers Squibb Company and Pfizer Inc. met all primary and secondary endpoints in a Phase III study determining safety and efficacy, the companies jointly announced this morning.
The Phase III ANNEXA-A study showed andexanet alfa, an investigational drug that received a breakthrough therapy designation from the U.S. Food and Drug Administration (FDA), significantly reduced the level of free unbound Eliquis in the plasma and restored thrombin generation to normal. Eliquis (apixaban) is an oral selective Factor Xa inhibitor.
By inhibiting Factor Xa, a key blood-clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis, which was co-developed by Bristol-Meyers Squibb, is approved for multiple indications in the U.S. based on efficacy and safety data.
Andexanet alfa is a modified human Factor Xa molecule that acts as a decoy to target and sequester with high specificity both oral and injectable Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal hemostatic processes.
The drug is administrated intravenously and is followed by a continuous two-hour infusion to sustain the reversal of anticoagulation activity of the Factor Xa inhibitor Eliquis (apixaban) in healthy volunteers ages 50-75 years. Andexanet alfa produced rapid reversal of the anticoagulant effect of Eliquis, as measured by anti-Factor Xa activity, the study showed.
John T. Curnutte, executive vice president, research and development for Portola, said the results of the study are significant to meet varying clinical needs.
"These Phase 3 findings demonstrate that andexanet alfa can rapidly reverse anticoagulant activity for a short or sustained period of time and that anticoagulant activity can be reinitiated following discontinuation of the infusion,” Curnutte said in a statement.
“The results to date across our Phase II and Phase III andexanet alfa studies with both oral and injectable Factor Xa inhibitors suggest that andexanet alfa is the only investigational reversal agent to clinically show meaningful reversal of Factor Xa anticoagulant activity. There is an increasing number of patients on Factor Xa inhibitors who may need their anticoagulant reversed because they are bleeding or require surgery.”
News of the successful study sent Portola’s stock climbing this morning. The stock was trading at $47.10, up 5 percent over its opening price of $45.07. Over the past month the company stock has grown by 16.7 percent
Anticoagulants are often used to treat or reduce the risk of blood clots from forming, some of which can be life threatening.
“In patients who experience a major bleeding event or require emergency surgery, there is a need to stop the blood thinning effects of an anticoagulant, In this study, andexanet alfa was shown to rapidly reverse the anticoagulant effects of Eliquis,” Rory O'Connor, Pfizer’s head of Global Medical Affairs, Global Innovative Pharmaceuticals Business said in a statement.
Portola plans to submit data from the ANNEXA-A (apixaban) and ANNEXA-R (rivaroxaban) studies, and initial data from a Phase 4 study, as part of its Biologics License Application to the FDA under an Accelerated Approval pathway by the end of 2015.
In February Portola announced andexanet alfa was granted orphan drug designation by the FDA's Office of Orphan Products Development for reversing the anticoagulant effect of direct or indirect Factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery. Currently, there is no approved antidote for these patients.
The FDA's Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that currently affect fewer than 200,000 people in the United States.
As Rumors Swirl About GlaxoSmithKline Bid, Who Could Suitors Be?
Rumors are swirling that Swiss-based Roche and U.S.-based Johnson & Johnson are eying the U.K. company for approximately $143 billion. But Roche and J&J aren’t the only companies though who have been thought could go after the elephant that is Glaxo.
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So BioSpace wants to ask our readers again what they predict for this new dealmaking bonanza. Will Glaxo go—and if so, to whom?