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Portola Pharmaceuticals to Present Multiple Abstracts at the 61st American Society of Hematology (ASH) Annual Meeting
- Cerdulatinib Interim Phase 2a Data Highlight Efficacy and Safety Results in Patients with Heavily Pre-Treated T-Cell Malignancies and Follicular Lymphoma -
- Also Accepted: Oral and Poster Presentations on Andexxa® In Vitro Data -

SOUTH SAN FRANCISCO, Calif., Nov. 6, 2019 /PRNewswire/ -- Portola Pharmaceuticals, Inc.® (NASDAQ: PTLA) today announced that new interim results from the Company's ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, will be presented at the 2019 American Society of Hematology (ASH) Annual Meeting, December 7-10, 2019, in Orlando, Fla. Presentations include an oral session featuring data on cerdulatinib in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), as well as a poster highlighting data in patients with relapsed/refractory follicular lymphoma (FL) receiving cerdulatinib alone or in combination with rituximab.

Portola Pharmaceuticals, Inc. Logo (PRNewsfoto/Portola Pharmaceuticals, Inc.®)

The Company will also present new in vitro data on its Factor Xa inhibitor reversal agent Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] (USAN: andexanet alfa) related to its effect on thrombin generation in bleeding patients, an in vitro comparison with prothrombin complex concentrates (PCCs), and its effect on modified anti-Factor Xa (FXa) assays in two oral sessions and one poster session, respectively.

"We are pleased to present data on two Portola medicines – cerdulatinib and Andexxa – at the ASH Annual Meeting," said Jeff Myers, M.D., Portola's interim chief medical officer. "We look forward to building on the body of scientific evidence for cerdulatinib as we move toward initiating our planned registrational trial, CELTIC-1, in patients with relapsed/refractory peripheral T-cell lymphoma in the coming months."

Key abstract presentations include:

Oral Presentations

  • A Phase 2 Study of the Dual SYK/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma (Abstract #466)
     
    Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Novel Therapies in Peripheral T-cell Lymphomas
    Presenter: Steven M. Horwitz, M.D., Memorial Sloan Kettering Cancer Center, New York, NY
    Date and Time: Sunday, December 8, 2019, at 12:45 p.m. EST
    Location: Orange County Convention Center, Valencia D (W415D), Level 4
     
     
  • Effects of Andexanet Alfa on Thrombin Generation in Bleeding Associated With Factor Xa Inhibitor(Abstract #711)
     
    Session: 332. Anticoagulation and Antithrombotic Therapy: Bleeding Outcomes
    Presenter: Michiel Coppens, M.D., Ph.D., Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
    Date and Time: Monday, December 9, 2019, at 3:15 p.m. EST
    Location: Orange County Convention Center, W414AB, Level 4
     
     
  • Prothrombin Complex Concentrates (PCCs) Have Limited Effect on TF-Initiated Thrombin Generation in FXa Inhibitor-Anticoagulated Plasma: In Vitro Comparison between Direct Reversal By Andexanet Alfa and "Work Around" By PCCs (Abstract #713)
     
    Session: 332. Anticoagulation and Antithrombotic Therapy: Bleeding Outcomes
    Presenter: Genmin Lu, M.D., Portola Pharmaceuticals, Inc., South San Francisco, CA
    Date and Time: Monday, December 9, 2019, at 3:45 p.m. EST
    Location: Orange County Convention Center, W414AB, Level 4

Poster Presentations

  • Modified Anti-FXa Assays for Measuring the Residual Activity of Apixaban and Rivaroxaban in Andexanet Alfa-Containing Samples on the ACL TOP Family Coagulation Analyzers (Abstract #1153)
     
    Session: 332. Anticoagulation and Antithrombotic Therapy: Poster I
    Presenter: Anuja Khan, Ph.D., Research and Development, Instrumentation Laboratory, Bedford, MA
    Date and Time: Saturday, December 7, 2019, from 5:30 – 7:30 p.m. EST
    Location: Orange County Convention Center, Hall B, Level 2

  • Rapid and Durable Responses with the SYK/JAK Inhibitor Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular Lymphoma—Alone or in Combination with Rituximab (Abstract #3981)
     
    Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
    Presenter: Paul A. Hamlin, M.D., medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
    Date and Time: Monday, December 9, 2019, from 6:00 – 8:00 p.m. EST
    Location: Orange County Convention Center, Hall B, Level 2

Full session details and presentation listings for ASH 2019 are available at: https://ash.confex.com/ash/2019/webprogram/start.html.

About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (SYK) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both SYK (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival.

The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.

IMPORTANT SAFETY INFORMATION FOR ANDEXXA [coagulation factor Xa (recombinant), inactivated-zhzo]

BOXED WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST AND SUDDEN DEATHS

See full prescribing information for complete boxed warning

Treatment with Andexxa has been associated with serious and life‑threatening adverse events, including:

  • Arterial and venous thromboembolic events
  • Ischemic events, including myocardial infarction and ischemic stroke
  • Cardiac arrest
  • Sudden deaths

Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.

Indication
Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] is a recombinant modified human Factor Xa (FXa) protein indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis in patients.

Limitation of Use 
Andexxa has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban or rivaroxaban.

SELECT IMPORTANT SAFETY INFORMATION

Thromboembolic and Ischemic Risk
The thromboembolic and ischemic risks were assessed in 185 patients who received the Generation 1 product and in 124 patients who received the Generation 2 product. The median time to first event was six days, and patients were observed for these events for 30 days following Andexxa infusion. Of the 86 patients who received Generation 1 product and were re-anticoagulated prior to a thrombotic event, 11 (12.7%) patients experienced a thromboembolic event, ischemic event, cardiac event or death.

Monitor patients treated with Andexxa for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with Andexxa.

The safety of Andexxa has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with Andexxa. Safety of Andexxa also has not been evaluated in patients who received prothrombin complex concentrates, recombinant Factor VIIa, or whole blood products within seven days prior to the bleeding event.

Re-elevation or Incomplete Reversal of Anti-FXa Activity
The time course of anti-FXa activity following Andexxa administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients. Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the Andexxa bolus. This decrease was sustained through the end of the Andexxa continuous infusion. The anti-FXa activity returned to the placebo levels approximately two hours after completion of a bolus or continuous infusion. Subsequently, the anti-FXa activity decreased at a rate similar to the clearance of the FXa inhibitors.

Thirty-eight patients who received the Generation 1 product were anticoagulated with apixaban and had baseline levels of anti-FXa activity > 150 ng/mL. Nineteen of these 38 (50%) patients experienced a > 93% decrease from baseline anti-FXa activity after administration of Andexxa. Eleven patients who were anticoagulated with rivaroxaban had baseline anti-FXa activity levels > 300 ng/mL. Five of the 11 patients experienced a > 90% decrease from baseline anti-FXa activity after administration of Andexxa. Anti-FXa activity levels for patients who received the Generation 2 product were not available.

Adverse Reactions
The most common adverse reactions (≥ 5%) in patients receiving Andexxa were urinary tract infections and pneumonia.

The most common adverse reactions (≥ 3%) in healthy volunteers treated with Andexxa were infusion-related reactions.

Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. Using an electrochemiluminescence (ECL)-based assay, 145 Generation 1 Andexxa-treated healthy subjects were tested for antibodies to Andexxa as well as antibodies cross-reacting with Factor X (FX) and FXa. Low titers of anti-Andexxa antibodies were observed in 26/145 healthy subjects (17%); 6% (9/145) were first observed at Day 30 with 20 subjects (14%) still having titers at the last time point (days 44 to 48). To date, the pattern of antibody response in patients in the ANNEXA-4 study has been similar to that observed in healthy volunteers with 6% (6/98) of the patients having antibodies against Andexxa. None of these anti-Andexxa antibodies were neutralizing. No antibodies cross-reacting with FX or FXa were detected in healthy subjects (0/145) or in bleeding patients (0/98) to date. There is insufficient data to assess for the presence of anti-Andexxa antibodies for subjects received the Generation 2 product.

About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a global, commercial-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics that could significantly advance the fields of thrombosis and other hematologic conditions. The Company's first two commercialized products are Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo], marketed in Europe as Ondexxya® (andexanet alfa), and Bevyxxa® (betrixaban). The company also is advancing cerdulatinib, a SYK/JAK inhibitor being developed for the treatment of hematologic cancers. Founded in 2003 in South San Francisco, California, Portola has operations in the United States and Europe.

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 Portola's long-term strategy to build awareness of the clinical data supporting Andexxa, and become the standard of care for the patients taking Factor Xa inhibitors who may require a reversal agent and the potential benefit of Andexxa. Risks that contribute to the uncertain nature of the forward-looking statements include: the risk that physicians, patients and payers may not see the benefits of utilizing Andexxa for the indications for which it is approved; our ability to continue to manufacture our products and to expand approved manufacturing facilities; the possibility of unfavorable results from additional clinical trials involving Andexxa; our ability to grow our commercial operations in the EU and generate product revenue within projected timelines and budget; the risk that we may not obtain additional regulatory approvals necessary to expand or maintain approved indications for Andexxa; our expectation that we will incur losses for the foreseeable future and will need additional funds to finance our operations; the accuracy of our estimates regarding expenses and capital requirements; our ability to successfully build a hospital-based sales force and commercial infrastructure; our ability to obtain and maintain intellectual property protection for our product candidates; our ability to retain key scientific or management personnel and general market conditions. 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. 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.

SOURCE Portola Pharmaceuticals, Inc.®

For further information: Investors, Jennifer Zibuda, Portola Pharmaceuticals, IR@portola.com; Media, Christina Khoury-Folkens, Pure Communications, ckhoury@purecommunications.com