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Portola Pharmaceuticals Announces Interim Results from Ongoing Phase 3b/4 ANNEXA-4™ Study of Factor Xa Inhibitor Antidote AndexXa™ (andexanet alfa) in Patients with Acute Major Bleeding
--AndexXa Rapidly Reversed Anticoagulant Effect of Factor Xa Inhibitors; Excellent or Good Hemostasis Was Achieved in 79 Percent of Patients Over 12 Hours--
--Data Presented in Late-Breaking Science Hot Line Session at
--Webcast with ANNEXA-4 Executive Committee Members Today at
“In this preliminary analysis, AndexXa was effective in rapidly reversing anti-Factor Xa inhibitor activity and restoring normal blood clotting in real-world patients with Factor Xa inhibitor-related bleeding. Based on these interim results, we believe that ANNEXA-4 is on track to achieve its co-primary efficacy endpoints upon study completion,” said
Factor Xa inhibitors are associated with a decreased risk of intracranial hemorrhage compared to warfarin, however the consequences are similar and can be fatal. In large randomized trials, the 30-day mortality rate in Factor Xa inhibitor patients with intracranial hemorrhage (ICH) exceeds 40 percent.
The interim results from all 67 patients who received AndexXa showed that the antidote was not associated with any infusion reactions, and no patients developed antibodies to Factor Xa or Factor X or neutralizing antibodies to AndexXa. During the 30-day follow-up period, thrombotic events occurred in 12 patients (18 percent), and death occurred in 10 patients (15 percent). These events occurred within the range expected in this population given the severity of the bleeding, their underlying thrombotic risk, and the low percentage who restarted anticoagulant therapy following their bleeding episode.
“The ANNEXA-4 interim results are preliminary yet encouraging because the percentage of patients who have achieved excellent or good hemostasis is higher than the co-primary endpoint threshold of above 50 percent defined in the study protocol,” said
ANNEXA-4 Study Design
ANNEXA-4 is a global, single-arm, open-label clinical trial designed to evaluate AndexXa, a
ANNEXA-4 Interim Results
The interim results included safety data from 67 patients who experienced life-threatening gastrointestinal bleeding (49 percent), intracranial bleeding (42 percent) or bleeding at another site (9 percent) within 18 hours of administration of apixaban (31 patients), rivaroxaban (32 patients) or enoxaparin (4 patients).
The efficacy population included only those 47 patients whose bleed severity met the specific inclusion criteria, as determined by an independent adjudication committee, and whose baseline anti-Factor Xa activity was substantially elevated. The interim efficacy results showed the following:
- AndexXa rapidly and substantially reversed anti-Factor Xa activity, and these levels were sustained for the duration of administration. Following the bolus dose, median anti-Factor Xa activity decreased by 89 percent from baseline for patients on rivaroxaban and by 93 percent for patients on apixaban, and was sustained at similar levels for the duration of the two-hour infusion.
- AndexXa was associated with normalization of blood clotting and cessation of bleeding. The independent adjudication committee determined that 37 of 47 patients (79 percent) achieved excellent or good hemostasis. Among patients with gastrointestinal bleeding, 84 percent had excellent or good hemostasis as did 80 percent of patients with intracranial bleeding. Hemostatic efficacy was similar for patients on apixaban (75 percent) and rivaroxaban (81 percent).
Investor Event Webcast Information
Members of Portola’s senior management team, together with Dr.
About the Need for a Factor Xa Inhibitor Antidote
Annually, 1 to 4 percent of patients treated with Factor Xa inhibitors may experience major bleeding, and an additional 1 percent may require emergency surgery. Commensurate with the increase in the use of Factor Xa inhibitors -- for stroke prevention in atrial fibrillation; treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism; and prevention of DVT following knee or hip replacement surgery -- the number of hospital admissions due to bleeding associated with these agents continues to grow. In
AndexXa, an investigational drug, 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 potentially allowing for the restoration of normal hemostatic processes. AndexXa is the first compound being studied as an antidote for Factor Xa inhibitors that directly and specifically reverses anti-Factor Xa activity – the anticoagulant mechanism of these agents.
About Portola Pharmaceuticals, Inc.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the potential future regulatory approval of andexanet alfa and patient populations that could benefit from a Factor Xa inhibitor reversal agent. Risks that contribute to the uncertain nature of the forward-looking statements include the risk that we may be unable to satisfy regulatory requirements for such approval, we may be unable to manufacture andexanet alfa on a commercial scale, and we will need additional capital to fund our operations. These and other risks and uncertainties are described more fully in our most recent filings with the
Ana Kapor Portola Pharmaceuticalsir@portola.com Media Contact: Julie Normart W2O Groupjnormart@w2ogroup.com 415.946.1087