SOUTH SAN FRANCISCO, Calif.,
June 19, 2019 /PRNewswire/
-- Portola Pharmaceuticals, Inc.® (Nasdaq: PTLA)
today announced new interim results from the Company's ongoing
Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK
inhibitor, in patients with relapsed/refractory follicular lymphoma
(FL) receiving cerdulatinib alone or in combination with rituximab.
Data were presented this month in a poster session at the
24th Congress of the European Hematology Association
(EHA) in Amsterdam (June 13-16) and during an oral session today at
the 15th International Conference on Malignant Lymphoma
(ICML) in Lugano, Switzerland
(June 18-22).
Data included safety and efficacy findings for 40 patients who
received single agent cerdulatinib at 30 mg twice daily (with the
exception of two patients who initiated treatment at 35 mg) and 17
patients who received cerdulatinib at 30 mg twice daily in
combination with a standard dosing regimen of rituximab. The number
of prior treatment regimens including anti-CD20 antibody,
bendamustine and anthracyclines ranged from one to nine, with a
median of three.
Among the 40 patients in the cerdulatinib-only cohort, the
objective response rate (ORR) was 45%; five patients (13%) achieved
a complete response (CR), 13 patients (33%) achieved a partial
response (PR) and 10 patients (25%) achieved stable disease (SD).
Of the 27 patients with a PR or SD at first evaluation in the
single agent cerdulatinib cohort, 17 (63%) had a further reduction
in tumor volume at a subsequent efficacy evaluation. To date, 15 of
the 40 patients (38%) in the cerdulatinib-only cohort have been on
study drug for at least 10 months.
Among the 13 patients evaluated for efficacy in the cerdulatinib
and rituximab combination cohort, the ORR was 62%; one patient (8%)
achieved a CR, seven patients (54%) achieved a PR and five patients
(39%) achieved SD. To date, 10 of the 13 patients have been on
study drug from three to 10 months.
Cerdulatinib was generally well-tolerated and the safety profile
appeared similar in both cohorts. The most common adverse events
(AEs) occurring in ≥10% of patients were lipase increase (25%),
neutropenia (15%), amylase increase (13%) and diarrhea (10%). The
most common AEs in the combination cohort included lipase increase
(35%), neutropenia (23%) and diarrhea (12%). The lipase and amylase
increases were generally asymptomatic and not associated with
pancreatitis. Additionally, there was no emergence of late-stage
colitis, cardiac or liver abnormalities, or other evidence of
cumulative toxicity among patients in the single-agent cerdulatinib
arm.
"Despite recent advances, relapsed or refractory follicular
lymphoma remains a challenging and heterogeneous disease. Oral
therapies that can address multiple signaling pathways and overcome
chemoresistance without cumulative side effects are urgently
needed," said Paul Hamlin, M.D.,
medical director for the David H. Koch Center for Cancer Care at
Memorial Sloan Kettering Cancer Center. "Cerdulatinib
continues to show promise across a range of B- and T-cell
malignancies, and I am encouraged by these interim results,
indicating sustained clinical activity and good tolerability of
cerdulatinib in these follicular lymphoma patients."
"We are very encouraged by these early findings and look forward
to continuing to gather additional data that will further
characterize the safety and efficacy profile of cerdulatinib in
patients with relapsed/refractory follicular lymphoma," said
Jeff Myers, Portola's interim chief medical officer.
"Simultaneously, we are continuing to move forward with the
development of cerdulatinib in relapsed/refractory peripheral
T-cell lymphoma and plans to initiate a registrational trial by the
end of the year."
ICML Oral Presentation
Details
Wednesday, June 19,
2019 from 17:15 p.m. CEST/ 8:15 a.m. PDT
- 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 #30)
Presenter: Stephen Smith, M.D.,
of the University of Washington/Fred
Hutchinson Cancer Research Center.
Cerdulatinib has demonstrated broad clinical activity in both B-
and T-cell malignancies. At the American Society of Hematology
meeting in December 2018, the Company
presented an update on cerdulatinib's activity in
relapsed/refractory peripheral T-cell lymphoma (PTCL);
angioimmunoblastic T-cell lymphoma (AITL), a subset of PTCL; and
cutaneous T-cell lymphoma (CTCL). As of the November 1, 2018 cut-off date, the ORR in the
PTCL cohort was 34% with 27% achieving a CR. Among the subset of
patients in the PTCL cohort with AITL, the ORR was 57% with a CR of
50%. The ORR in the CTCL cohort was 26% with 7% of patients
achieving a CR. Importantly, rapid improvements in pruritus, or
severe itching – a common and often serious condition associated
with CTCL – were observed. Follow-up analysis of these cohorts is
ongoing with plans to start a registrational study in PTCL by the
end of the year.
About the Phase 2a Study
The Phase 2a, open-label
study was designed to assess the safety and efficacy of
cerdulatinib in patients with relapsed/refractory FL (alone or in
combination with rituximab), small lymphocytic lymphoma (SLL) and
specific subtypes of T-cell Non-Hodgkin Lymphoma, including PTCL,
AITL and CTCL.
Tumor response in the two cohorts evaluating patients with
relapsed/refractory FL was assessed by Lugano classification, with
treatment continued until disease progression or unacceptable
toxicity. Tumor response assessments were performed at the end of
cycle two and every three cycles thereafter.
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.
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 the anticipated development plan for
cerdulatinib. Risks that contribute to the uncertain nature of the
forward-looking statements include: the risk of unfavorable results
from additional clinical trials involving cerdulatinib; our ability
to successfully execute on our development strategy; the risk of
unfavorable regulatory developments; our expectation that we will
incur losses for the foreseeable future and will need additional
funds to finance our operations; the effects of competition; 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; and our ability to retain key scientific or management
personnel. 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 annual report on
Form 10-K and 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.
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SOURCE Portola Pharmaceuticals, Inc.®