This account is pending registration confirmation. Please click on the link within the confirmation email previously sent you to complete registration.
Need a new registration confirmation email? Click here
See Cramer's multi-million dollar portfolio for FREE and get his new book Get Rich Carefully! Learn More

Portola Pharmaceuticals Announces Additional Positive Phase 2 Proof-of-Concept Data For Andexanet Alfa (PRT4445*)

SOUTH SAN FRANCISCO, Calif., Nov. 11, 2013 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) today announced initial results from a Phase 2 proof-of-concept study of andexanet alfa, its investigational Factor Xa inhibitor antidote, in healthy volunteers who were administered the Factor Xa inhibitor XARELTO ® (rivaroxaban). Results from the first two dosing cohorts of the study demonstrated that andexanet alfa is able to dose-dependently reverse the anticoagulant effects of XARELTO ®. In addition, no serious adverse events were reported. These data, as well as data from additional cohorts evaluating higher doses of andexanet alfa, will be presented in a poster session on December 9, 2013 at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition, which is being held in New Orleans from December 7-10, 2013.

Andexanet alfa is being developed as a potential first-in-class, universal antidote for patients who experience an uncontrolled bleeding episode or who require emergency surgery while being anticoagulated with a Factor Xa inhibitor. Registration-enabling studies are planned to begin in 2014 as part of a potential Accelerated Approval pathway to address the important unmet need due to a lack of an approved antidote.

"We are pleased with these initial data demonstrating a dose-dependent reversal of the Factor Xa inhibitor, XARELTO ® . These findings are consistent with what we expect from andexanet's mechanism of action, and the dose-dependent activity we have seen with andexanet alfa in our prior Phase 2 study with Eliquis ®. We look forward to presenting data on additional cohorts evaluating higher doses of andexanet in healthy volunteers treated with XARELTO ® at the ASH meeting in December," said John T. Curnutte, M.D., Ph.D., executive vice president of research and development for Portola. "We are now increasingly confident that the positive proof-of-concept data shown with both Eliquis and XARELTO ® to date will help us determine an appropriate and effective dosing regimen for all oral Factor Xa inhibitors and enoxaparin for use in the conduct of our planned pivotal registration studies."

This randomized, placebo-controlled, double-blind, cohort dose-escalation Phase 2 proof-of-concept study treated healthy volunteers with an oral dose of XARELTO ® at 20 mg qd for 6 days and then randomized them in a 6:3 ratio to andexanet alfa in different dosing cohorts. The first two cohorts received a single IV bolus of andexanet alfa at 210 mg or 420 mg, respectively. Within two minutes following completion of the 210 mg and 420 mg bolus of andexanet alfa, anti-Factor Xa activity decreased dose-dependently by 20 percent and 53 percent, respectively. XARELTO ® -induced inhibition of thrombin generation and prolongation of both prothrombin time and activated clotting time were also rapidly reversed by andexanet alfa in a dose-dependent manner. Interim safety data showed that andexanet alfa was well tolerated, with no thrombotic events, or serious or severe adverse events reported. The abstract with these data is currently available on the ASH website.

Need for Reversal Agent for Factor Xa Inhibitors Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions in the G7 countries, and the anticoagulant market is expected to continue to grow with the adoption of novel oral anticoagulants. Clinical trial results suggest that, depending on their underlying medical condition, annually between 1 and 4 percent of these patients will experience major bleeding and an additional 1 percent will require emergency surgery. Based on these data and projected use of Factor Xa inhibitors, the Company estimates there could be approximately 500,000 hospital visits each year by patients who would benefit from an antidote by the year 2020. Currently, there is no antidote or reversal agent approved for use against Factor Xa inhibitors. Leading clinicians have identified, and the United States Food and Drug Administration (FDA) has recognized, the lack of an effective reversal agent for Factor Xa inhibitors as a significant unmet medical need.

Andexanet Alfa Clinical Development Program

Portola has entered into clinical collaboration agreements with all of the manufacturers of currently approved Factor Xa inhibitors, including Bristol-Myers Squibb and Pfizer ( Eliquis ®  [apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (XARELTO ® [rivaroxaban]), and Daiichi Sankyo (Lixiana ® [edoxaban]), while retaining all rights to the program. The Company is currently conducting a series of Phase 2 proof-of-concept studies in healthy volunteers to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of andexanet alfa after dosing of a direct or indirect Factor Xa inhibitor, including Eliquis ®, XARELTO ®, Lovenox ® (enoxaparin), Lixiana ® and Portola's investigational oral Factor Xa inhibitor, betrixaban.

About Andexanet Alfa (PRT4445*)

Andexanet alfa is a novel recombinant, modified Factor Xa molecule that has the potential to be the first universal antidote to reverse the effects of Factor Xa inhibitors in patients who suffer an uncontrolled bleeding episode or require emergency surgery. Andexanet alfa is similar to native Factor Xa, but has been modified to restrict its biological activity, such as its ability to cleave thrombin, an enzyme involved in the clotting cascade. Andexanet alfa acts as a Factor Xa decoy that binds and sequesters direct Factor Xa inhibitors in the blood. Once bound to andexanet alfa, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa. The native Factor Xa should then be available to participate in the coagulation process and restore hemostasis.

Stock quotes in this article: PTLA 

Select the service that is right for you!

Action Alerts PLUS
Try it NOW

Jim Cramer and Stephanie Link actively manage a real portfolio and reveal their money management tactics while giving advanced notice before every trade.

Product Features:
  • $2.5+ million portfolio
  • Large-cap and dividend focus
  • Intraday trade alerts from Cramer
  • Weekly roundups
TheStreet Quant Ratings
Try it NOW
Only $49.95/yr

Access the tool that DOMINATES the Russell 2000 and the S&P 500.

Product Features:
  • Buy, hold, or sell recommendations for over 4,300 stocks
  • Unlimited research reports on your favorite stocks
  • A custom stock screener
  • Upgrade/downgrade alerts
Stocks Under $10
Try it NOW

David Peltier, uncovers low dollar stocks with extraordinary upside potential that are flying under Wall Street's radar.

Product Features:
  • Model portfolio
  • Stocks trading below $10
  • Intraday trade alerts
  • Weekly roundups
Dividend Stock Advisor
Try it NOW

Jim Cramer's protege, David Peltier, identifies the best of breed dividend stocks that will pay a reliable AND significant income stream.

Product Features:
  • Diversified model portfolio of dividend stocks
  • Alerts when market news affect the portfolio
  • Bi-weekly updates with exact steps to take - BUY, HOLD, SELL
Real Money Pro
Try it NOW

All of Real Money, plus 15 more of Wall Street's sharpest minds delivering actionable trading ideas, a comprehensive look at the market, and fundamental and technical analysis.

Product Features:
  • Real Money + Doug Kass Plus 15 more Wall Street Pros
  • Intraday commentary & news
  • Ultra-actionable trading ideas
Options Profits
Try it NOW

Our options trading pros provide daily market commentary and over 100 monthly option trading ideas and strategies to help you become a well-seasoned trader.

Product Features:
  • 100+ monthly options trading ideas
  • Actionable options commentary & news
  • Real-time trading community
  • Options TV
To begin commenting right away, you can log in below using your Disqus, Facebook, Twitter, OpenID or Yahoo login credentials. Alternatively, you can post a comment as a "guest" just by entering an email address. Your use of the commenting tool is subject to multiple terms of service/use and privacy policies - see here for more details.
DOW 16,501.65 0.00 0.00%
S&P 500 1,878.61 +3.22 0.17%
NASDAQ 4,148.3380 +21.3710 0.52%

Brokerage Partners

Rates from

  • Mortgage
  • Credit Cards
  • Auto
Advertising Partners

Free Newsletters from TheStreet

My Subscriptions:

After the Bell

Before the Bell

Booyah! Newsletter

Midday Bell

TheStreet Top 10 Stories

Winners & Losers

Register for Newsletters
Top Rated Stocks Top Rated Funds Top Rated ETFs