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Portola Pharmaceuticals Presents Updated Data From Ongoing Phase 1/2a Study of Dual Kinase Inhibitor Cerdulatinib
The results to be presented at
"The clinical activity that we have seen with cerdulatinib in this hematologic cancer study is particularly notable given that these patients have advanced disease and have failed previous therapies," said
"These preliminary results from the ongoing dose-escalation Phase 1 part of the study, including partial responses, provide additional evidence that cerdulatinib is active and well tolerated in patients with hematologic cancers who have failed multiple therapies," said
Additional findings from the Phase 1 part of the study to be presented at
- Cerdulatinib significantly reduced multiple serum proteins in blood that are markers of inflammation.
- Significant correlations were observed between tumor response and inhibition of serum markers of inflammation.
- Cerdulatinib selectively and dose-dependently inhibited SYK/JAK signaling, with maximal inhibition greater than 80 percent.
- Once-daily dosing of cerdulatinib was supported by pharmacokinetic data.
New Treatment Options Needed for CLL and FL Patients
Current treatment options for patients who fail standard therapies for CLL, SLL and FL are limited. A recent article in Bloodi highlights the need for additional therapies for CLL in particular. An analysis of patients with relapsed/refractory CLL who were enrolled in clinical trials found that those whose disease progressed following treatment with the
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, SLL, FL or B-cell 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. It 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 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.
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
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
i Pinilla-Ibarz J, Chavez JC. Life after ibrutinib? A new unmet need in CLL. Blood. 2015;125;2013-2014.
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Michele Mantynen Portola Pharmaceuticalsir@portola.com Media Contact: Jani BerganBrewLife firstname.lastname@example.org