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Portola Pharmaceuticals Submits NDA to U.S. FDA for Betrixaban for Extended Duration Prophylaxis of Venous Thromboembolism in Acute Medically Ill Patients

SOUTH SAN FRANCISCO, Calif., Oct. 25, 2016 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals Inc.® (Nasdaq:PTLA) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval to market betrixaban for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE. Betrixaban, an FDA Fast Track-designated investigational drug, is an oral, once-daily Factor Xa inhibitor anticoagulant.

“Hospitalized acute medically ill patients are at significant risk of experiencing a potentially life-threatening VTE event, both during their stay and after discharge, especially within the first four weeks. Yet, no drug is approved in the United States for extended use to prevent VTE in these patients. We are committed to bringing betrixaban to market to address this urgent unmet medical need,” said John Curnutte, M.D. Ph.D., executive vice president, research and development at Portola. “If approved, betrixaban would be the first anticoagulant indicated for the prevention of VTE in acute medically ill patients both during hospitalization and for an extended period after the patient returns home.”

An estimated 22.5 million acute medically ill patients in the G7 countries are at risk of developing VTE, which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), either while in the hospital or following discharge. Each year, more than 1 million VTE events and 150,000 VTE-related deaths occur in acute medically ill patients in the G7 countries, despite the standard use of injectable enoxaparin and other heparins in the hospital. More than half of VTE events occur after the patient is discharged from the hospital. However, no anticoagulant, including enoxaparin or any of the marketed oral Factor Xa inhibitors, is approved for extended VTE prophylaxis for acute medically ill patients who are hospitalized.

The NDA for betrixaban is supported by data from the pivotal Phase 3 APEX Study, which 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. 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.

“The submission of the betrixaban NDA as planned is an important accomplishment for Portola and our regulatory and clinical teams as a first step towards a potential approval in 2017,” said Bill Lis, chief executive officer of Portola. “Based on the totality of data from the pivotal Phase 3 APEX study, there is strong support among the medical community for the use of betrixaban in preventing VTE in medically ill patients. We believe our dossier with the APEX Study as the basis shows clear evidence of betrixaban’s efficacy and safety. We look forward to working with the FDA as they review our application.”

Portola expects a response from the FDA within 60 days as to whether the NDA is complete and acceptable for filing. The Company plans to submit a Marketing Authorization Application for approval of betrixaban in the EU by the end of this year.

About the Need for an Oral Anticoagulant for Extended-Duration Prevention of VTE in Acute Medically Ill Patients

Acute medically ill patients are those hospitalized for serious, common medical conditions, including heart failure, stroke, infection and pulmonary disease. Because of their underlying disorder or immobilization during hospitalization, they are at increased risk of VTE, a serious and potentially life-threatening blood clot (thrombus). VTE includes both DVT, a blood clot in a deep vein in the leg, and PE, a blood clot in a deep vein in the leg that breaks loose and travels to the lungs, where it lodges, blocking the pulmonary artery or one of its branches, where it can be fatal.

VTE is a major cause of preventable morbidity and mortality and re-hospitalization in the acute medically ill patient population. The incidence of VTE in acute medically ill patients has been reported to be at least as high as in patients undergoing general surgery.i Approximately 2.5 percent of high-risk medical patients will experience a symptomatic VTE or VTE-related death.ii Hospitalized patients are at significant risk of experiencing VTE events both during their stay and after discharge.iii They remain at increased risk for up to three months following discharge, with the peak incidence occurring within the first four weeks.iv,v

About Betrixaban

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.

About Portola Pharmaceuticals, Inc.

Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that could significantly advance the fields of thrombosis and other hematologic diseases. The Company is advancing three programs, including betrixaban, an oral, once-daily Factor Xa inhibitor; AndexXa™ (andexanet alfa), a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable Factor Xa inhibitor; and cerdulatinib, a Syk/JAK inhibitor in development to treat hematologic cancers. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions. For more information, visit www.portola.com and follow the Company on Twitter @Portola_Pharma.

Forward-looking Statements

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 timing of a response from the FDA to our NDA and our submission of a Marketing Authorization Application in the EU, and potential approval of betrixaban. Risks that contribute to the uncertain nature of the forward-looking statements include the risk that our data fail to demonstrate safety and efficacy to the satisfaction of the FDA or similar regulatory authorities outside the United States and the risk that the results from our APEX clinical trial may cause betrixaban regulatory approval to be delayed, more costly or not be obtained at all. These and other risks and uncertainties are described more fully in our most recent filings with the Securities and Exchange Commission, including our most recent quarterly report on Form 10-Q, which was filed on August 9, 2016. All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

i Turpie AGG, Leizorovicz A. Prevention of venous thromboembolism in medically ill patients: a clinical update. Postgrad Med J. 2006;82(974):806-809.
ii Spyropoulos AC, Anderson FA, FitzGerald G, Decousus H, Pini M, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
iii Amin AN, Varker H, Princic N, Lin J, Thompson S, et al. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med. 2012;7:231-8.
iv Heit JA, Melton LJ, Lohse CM, Petterson TM, Silverstein MD, et al. Incidence of venous thromboembolism in hospitalized patients vs. community residents. Mayo Clin Proc. 2001;76:1102-10.
v Cohen AT. Results from the VEG Registry. Presented at the 23rd Congress of the International Society on Thrombosis and Haemostasis 57th Annual SSC Meeting, July 23-28, 2011, Kyoto Japan.

Source: Portola Pharmaceuticals, Inc.

Posted: October 2016

betrixaban FDA Approval History

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