--Updated Safety and Efficacy Data From Phase 1 Part of Ongoing Phase 1/2a Study to be Presented--
--Company Opens Enrollment in Expansion Cohorts in Phase 2a Part of Study--
SOUTH SAN FRANCISCO, Calif., May 18, 2015 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that it will present updated safety and efficacy data from the Phase 1 part of its ongoing Phase 1/2a proof-of-concept study of cerdulatinib in patients with hematologic cancers who have failed multiple therapies. The data will be presented in a poster discussion session at the upcoming 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, which is taking place from May 29-June 2 in Chicago. The Company also announced that it has initiated two clinical expansion cohorts in the Phase 2a part of the study, which will enroll patients with chronic lymphocytic leukemia (CLL) or follicular lymphoma (FL) who have progressed or relapsed on other therapies. The Phase 1 part of the study is ongoing as the maximum tolerated dose has not yet been achieved.
Cerdulatinib is an oral, dual Syk-JAK kinase inhibitor that Portola is developing to treat patients with hematologic cancers, specifically those who have relapsed or who have not responded to prior therapies.
"We have demonstrated initial clinical proof-of-concept in the ongoing dose-escalation Phase 1 part of the study showing that cerdulatinib is active and well tolerated. We have seen partial responses with this unique dual pathway anti-cancer agent and clinical activity in patients who failed or could not tolerate prior therapy with BTK and PI3K kinase inhibitors," said John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola. "Based on these promising preliminary data, we have advanced cerdulatinib to the next stage of clinical development to study larger expansion cohorts in the Phase 2a part of the study. We will evaluate two cohorts of patients with CLL or FL whose cancer has progressed or relapsed following treatment with multiple agents. These patients have limited treatment options. Our goal is to identify patient populations with significant unmet need in whom the inhibition of both Syk and JAK by cerdulatinib may provide clinical benefit."
The cerdulatinib abstract is now available at abstracts.asco.org. Details regarding the cerdulatinib poster presentation, which will include additional data not currently available in the published abstract, follow.
Abstract Title: Phase 1 open-label dose escalation study of the dual SYK/JAK inhibitor cerdulatinib (PRT062070) in patients with relapsed/refractory B-cell malignancies: Safety profile and clinical activity (abstract #8531; poster board #348)
Presenter: Ian W. Flinn, M.D., Ph.D., director, Hematologic Malignancies Research, Program, Sarah Cannon Research Institute, Memphis
Session Name: Poster Discussion Session -- Lymphoma and Plasma Cell Disorders
Session Date, Time and Location: Sunday, May 31, from 4:30-5:45 p.m. CT; S Hall A, McCormick Place
About the Phase 1/2a Study
The open-label, multicenter, Phase 1/2a proof-of-concept study is assessing the safety, pharmacokinetics, pharmacodynamics and clinical activity of oral cerdulatinib in patients with CLL and non-Hodgkin lymphoma. In the multi-dose, dose-escalation Phase 1 part of the study, cerdulatinib is being administered orally once a day to sequential dose cohorts at increasing dose levels until the maximum tolerated dose is identified. The maximum tolerated dose has not yet been identified and the study is continuing.
The clinical expansion cohorts in the Phase 2a part of the study will evaluate the safety and efficacy of cerdulatinib in cancer types identified based on responses seen in the dose-escalation phase of the study. Two groups of up to 40 patients each will be enrolled in the clinical expansion cohorts. One group will include patients with CLL or small lymphocytic leukemia (SLL) whose disease has progressed following prior therapies. The other group will include patients with FL who have progressed or relapsed on prior therapies (such as rituximab and bendamustine).
Cerdulatinib is an oral, dual Syk-JAK inhibitor with a unique mechanism of action. It uniquely inhibits two key signaling pathways that promote cancer cell growth in certain hematologic malignancies: the B-cell receptor pathway via Syk and key cytokine receptors via JAK. With its dual pathway mechanism, cerdulatinib may be more effective in specific patients than a single pathway agent, such as those resistant to current therapies or those with known heterogeneous cellular mutations. Preclinical data suggested that cerdulatinib has anti-tumor activity in patients who did not adequately respond to, or relapsed on, other treatments due to defined mutations.
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 its three wholly-owned programs using novel biomarker and genetic approaches that may increase the likelihood of clinical, regulatory and commercial success of its potentially life-saving therapies. Portola's partnered programs are focused on developing selective Syk inhibitors for inflammatory conditions.
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor betrixaban is being evaluated in the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's distinct properties may have the potential to allow the agent to demonstrate efficacy without the significant increase in the rate of major bleeding that was seen in this patient population with other Factor Xa inhibitors. If approved, betrixaban could be the first anticoagulant for both hospital and post-discharge VTE prophylaxis and the standard of care in this large market of more than 20 million patients in the G7 countries alone.
Andexanet alfa, an FDA-designated breakthrough therapy, is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable Factor Xa inhibitor. Andexanet alfa has the potential to be a first-in-class antidote for anticoagulated patients who suffer a major bleeding episode or require emergency surgery. Portola has entered into Phase 3 clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the Phase 3 and Phase 4 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors) registration studies.
Portola's product candidate in the area of hematologic cancer, cerdulatinib, is an orally available molecule that uniquely inhibits two validated tumor proliferation pathways – spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being evaluated in a Phase 1/2a proof-of-concept study in patients with B cell leukemias or lymphomas with a focus on genetically-defined subtypes, as well as in patients who have failed therapy due to relapse or acquired mutations.
For more information, visit www.portola.com and follow the Company on Twitter @Portola_Pharma.
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 plans for future clinical studies and pursuit of an Accelerated Approval process for andexanet alfa, anticipated growth in the market for anticoagulants, the potential indications, efficacy, safety and activity of andexanet alfa, and the potential market and indications for its other product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to initiate and/or complete its clinical trials; the success of Portola's clinical trials and the demonstrated efficacy of Portola's product candidates thereunder; the accuracy of Portola's estimates regarding its expenses and capital requirements; Portola's ability to manufacture andexanet alfa; regulatory developments in the United States and foreign countries; Portola's ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Portola's most recent filings with the Securities and Exchange Commission, including its Annual Report on Form 10-Q, which was filed on May 7, 2015. All forward-looking statements contained in this press release speak only as of the date on which they were made. Portola undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.