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Portola Pharmaceuticals Announces Three Phase 3 APEX Substudy Results Showing Further Benefits of Treating Acute Medically Ill Patients with Extended-Duration Betrixaban
In a retrospective APEX substudy on stroke, researchers assessed the potential of extended-duration thromboprophylaxis with betrixaban compared with standard-dose enoxaparin to reduce the risk of stroke in hospitalized acute medically ill patients. The substudy found that extended-duration betrixaban significantly reduced all-cause stroke (0.54 percent for betrixaban vs. 0.97 percent for enoxaparin; RRR=44 percent, p=0.032) and ischemic stroke (0.48 percent for betrixaban vs. 0.91 percent for enoxaparin; RRR=47 percent, p=0.026) through 77 days of follow up. The results were presented today by
“Stroke is a potentially fatal complication, but little is known about the effectiveness of novel oral anticoagulants in preventing stroke among the acute medically ill patient population. We were encouraged to find that betrixaban was associated with a reduction in the risk of all-cause stroke within 30 to 60 days, which was driven predominantly by a reduction in ischemic stroke, without an increased risk of major bleeding,” said Dr. Gibson, APEX Executive Committee Member and Steering Committee Chairman; professor,
A second retrospective APEX substudy, presented today at AHA by
Lastly, in a poster session tomorrow,
Stroke Substudy (Abstract #277)
In this substudy, the mean age of study participants was 76 years, 45 percent were male, 13 percent had had a stroke, and 45 percent had congestive heart failure. Stroke events were adjudicated by an independent blinded-event adjudication committee and assessed through last patient contact. The findings showed that, among the 3,716 patients treated with extended-duration betrixaban and the 3,716 patients treated with standard-of-care enoxaparin:
- There were fewer all-cause strokes among those treated with betrixaban than enoxaparin through 77 days of follow-up (0.54 percent vs. 0.97 percent; p=0.032).
- There were fewer ischemic strokes among those treated with betrixaban than enoxaparin through 77 days of follow-up (0.48 percent vs. 0.91 percent; p=0.026).
- The composite endpoint of all-cause stroke and transient ischemic attack (TIA) was also reduced among study subjects treated with extended-duration betrixaban versus enoxaparin (0.65 percent vs. 1.10 percent; p=0.034).
- Among patients at highest risk for stroke – i.e., those who had a prior ischemic stroke or a history of congestive heart failure -- the risk of all-cause stroke was reduced with betrixaban compared with enoxaparin (0.72 percent vs. 1.48 percent; p=0.019), as was ischemic stroke (0.63 percent vs. 1.38 percent; p=0.014).
About the APEX Study
The pivotal Phase 3 APEX Study enrolled 7,513 patients at more than 450 clinical sites worldwide and assessed the superiority of extended-duration anticoagulation with oral betrixaban for 35-42 days compared with standard-duration injectable enoxaparin for 10+4 days in preventing VTE in high-risk acute medically ill patients. The primary efficacy endpoint was a composite of asymptomatic proximal DVT (deep vein thrombosis) (detected on ultrasound), symptomatic DVT (proximal or distal), non-fatal pulmonary embolism (PE) and VTE-related death. The primary safety endpoint was major bleeding through seven days after drug discontinuation.
Results showed that betrixaban reduced the incidence of VTE compared with enoxaparin at a p value approaching statistical significance (p=0.054) in the primary efficacy analysis subgroup of 3,870 patients with elevated D-dimer levels. It also significantly reduced VTE in several pre-specified analyses of the primary efficacy analysis subgroup as well as in the overall study population (p=0.006) of 7,513 patients. No statistical difference in major bleeding was observed between the betrixaban and enoxaparin arms in either of the primary analysis patient subgroup or in the overall study population.
Full results from the multicenter, randomized, active-controlled APEX Study were presented at the 62nd Annual
Betrixaban, an investigational drug, directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent life-threatening thrombosis. Betrixaban has distinct properties that may allow it to demonstrate clinical benefit without the significant imbalance in the risk of major bleeding seen with other agents in the class. These include a 19-25-hour half-life for once-daily dosing; a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability; low renal clearance; and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban has been given Fast Track designation by the
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 development of our product candidates, our regulatory applications and estimated timelines associated therewith. Risks that contribute to the uncertain nature of the forward-looking statements include: failure to obtain regulatory approval for one or more of our product candidates, our expectation that we will incur losses for the foreseeable future and will need additional funds to finance our operations; the results of our clinical trials related to the efficacy and safety of our product candidates; our potential inability to manufacture our product candidates on a commercial scale in a timely or cost-efficient manner; the accuracy of our estimates regarding expenses and capital requirements; regulatory developments in
i Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
Ana Kapor Portola Pharmaceuticalsir@portola.com Media Contact: Julie Normart W2O Groupjnormart@w2ogroup.com 415.946.1087