PHILADELPHIA, April 20, 2015 /PRNewswire/ -- Ibrutinib
(IMBRUVICA®) data presented yesterday by Pharmacyclics,
Inc. (NASDAQ: PCYC) at the American Association for Cancer Research
(AACR) Annual Meeting suggest that ibrutinib may be an effective
therapeutic option for pancreatic ductal adenocarcinoma (PDAC), as
shown in both a transgenic mouse model and an in-vivo model of
patient-derived xenograft (PDX) mice (grafts of tissue taken from a
pancreatic cancer patient and grafted into a mouse).1
These early, pre-clinical data show ibrutinib was associated with
potent anti-fibrotic activity and longer survival in the treated
mice. PDAC is a type of pancreatic cancer that is typically
characterized by a fibro-inflammatory reaction, which makes PDAC a
difficult disease to treat with current therapies. These data were
also published in the April
15th edition of Cancer Research.
IMBRUVICA is jointly developed and commercialized by Pharmacyclics
and Janssen Biotech, Inc.
"These results are very promising, particularly considering that
there is an urgent need for new treatment options for people living
with pancreatic adenocarcinoma, an aggressive disease with limited
therapies," said Laura Soucek,
Ph.D., Principal Investigator for the Mouse Models of Cancer
Therapies Laboratory at the Vall d'Hebron Institute of Oncology
(VHIO) in Barcelona, Spain and an
investigator for the study. "These results are compelling and
additional research is needed to determine the therapeutic impact
of ibrutinib in patients with pancreatic cancer."
PDAC is the most common form of pancreatic cancer and is often
associated with poor prognosis.2,3 PDAC is the fourth
leading cause of cancer death in the
United States, with an average survival time of less than
one year after diagnosis. There are approximately 45,000 newly
diagnosed patients every year, with the median age of 71 years at
diagnosis.2
"These promising preclinical data are encouraging due to the
poor outcomes currently seen with available therapies," said
Danelle James, M.D., M.S., Head of
Oncology at Pharmacyclics. "Novel treatment approaches are needed
for this devastating disease and we are encouraged by these
preclinical findings suggesting that ibrutinib may have a positive
impact on patients with pancreatic adenocarcinoma. We are committed
to continuing to investigate the potential utility of IMBRUVICA
across multiple histologies, including difficult-to-treat solid
tumors."
The study evaluated the use of ibrutinib versus a vehicle
control in two different preclinical mouse models of PDAC and found
treatment with ibrutinib not only dramatically reduced tumor cell
proliferation and inflammatory cell infiltration, but also was
associated with reductions in collagen deposition in the stroma of
the PDAC mice. The mice treated with ibrutinib also experienced
longer survival, particularly when the therapy was used in
combination with gemcitabine. Additional clinical research is
needed to fully understand the potential benefits of ibrutinib for
patients with PDAC.
Ibrutinib is currently being studied in pancreatic cancer. To
learn more about the clinical study, visit: www.clinicaltrials.gov
or call Pharmacyclics Medical Information at 877-877-3536.
About IMBRUVICA
IMBRUVICA is currently approved
for the treatment of patients with chronic lymphocytic leukemia
(CLL) who have received at least one prior therapy, all CLL
patients (including treatment-naive) who have del 17p, a genetic
mutation that occurs when part of chromosome 17 has been lost, and
all patients (including treatment-naive) with Waldenstrom's
macroglobulinemia.4 IMBRUVICA is also approved
under accelerated approval for the treatment of patients with
mantle cell lymphoma (MCL) who have received at least one prior
therapy.4
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily
therapy that inhibits a protein called Bruton's tyrosine kinase
(BTK).4 IMBRUVICA was one of the first medicines to
receive U.S. FDA approval via the new Breakthrough Therapy
Designation pathway, and is the only product to have received three
Breakthrough Therapy Designations.
BTK is a key signaling molecule in the B-cell receptor signaling
complex that plays an important role in the survival and spread of
malignant B cells.4,5 IMBRUVICA blocks signals that tell
malignant B cells to multiply and spread
uncontrollably.4
IMBRUVICA is being studied alone and in combination with other
treatments in several blood cancers. Over 5,100 patients have been
treated in clinical trials of IMBRUVICA conducted in 35 countries
by more than 800 investigators. Currently, 13 Phase III trials have
been initiated with IMBRUVICA and 60 trials are registered on
www.clinicaltrials.gov.
To learn more about the medical terminology used in this news
release, please visit
http://stedmansonline.com/.
INDICATIONS
IMBRUVICA is indicated to treat people with:
- Chronic lymphocytic leukemia (CLL) who have received at least
one prior therapy
- Chronic lymphocytic leukemia (CLL) with 17p deletion
- Waldenstrom's macroglobulinemia
- Mantle cell lymphoma (MCL) who have received at least one prior
therapy – accelerated approval was granted for this indication
based on overall response rate. Continued approval for this
indication may be contingent upon verification of clinical benefit
in confirmatory trials.
Patients taking IMBRUVICA for CLL or WM should take 420 mg taken
orally once daily (or three 140 mg capsules once daily).
Patients taking IMBRUVICA for MCL should take 560 mg taken
orally once daily (or four 140 mg capsules once daily).
Capsules should be taken orally with a glass of water. Capsules
should be taken whole. Do not open, break, split or chew the
capsules.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage - Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Grade 3 or higher
bleeding events (subdural hematoma, gastrointestinal bleeding,
hematuria, and post-procedural hemorrhage) have occurred in up to
6% of patients. Bleeding events of any grade, including bruising
and petechiae, occurred in approximately half of patients treated
with IMBRUVICA®.
The mechanism for the bleeding events is not well understood.
IMBRUVICA® may increase the risk of hemorrhage in
patients receiving antiplatelet or anticoagulant therapies.
Consider the benefit-risk of withholding IMBRUVICA® for
at least 3 to 7 days pre and post-surgery depending upon the type
of surgery and the risk of bleeding.
Infections - Fatal and non-fatal infections have occurred
with IMBRUVICA® therapy. Grade 3 or greater infections
occurred in 14% to 26% of patients. Cases of progressive multifocal
leukoencephalopathy (PML) have occurred in patients treated with
IMBRUVICA®. Monitor patients for fever and infections
and evaluate promptly.
Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias
including neutropenia (range, 19 to 29%), thrombocytopenia (range,
5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated
with IMBRUVICA®. Monitor complete blood counts
monthly.
Atrial Fibrillation - Atrial fibrillation and atrial
flutter (range, 6 to 9%) have occurred in patients treated with
IMBRUVICA®, particularly in patients with cardiac risk
factors, acute infections, and a previous history of atrial
fibrillation. Periodically monitor patients clinically for atrial
fibrillation. Patients who develop arrhythmic symptoms (e.g.,
palpitations, lightheadedness) or new-onset dyspnea should have an
ECG performed. If atrial fibrillation persists, consider the risks
and benefits of IMBRUVICA® treatment and dose
modification.
Second Primary Malignancies - Other malignancies (range,
5 to 14%) including non-skin carcinomas (range, 1 to 3%) have
occurred in patients treated with IMBRUVICA®. The most
frequent second primary malignancy was non-melanoma skin cancer
(range, 4 to 11%).
Tumor Lysis Syndrome - Tumor lysis syndrome has been
reported with IMBRUVICA® therapy. Monitor patients
closely and take appropriate precautions in patients at risk for
tumor lysis syndrome (e.g. high tumor burden).
Embryo-Fetal Toxicity - Based on findings in animals,
IMBRUVICA® can cause fetal harm when administered to a
pregnant woman. Advise women to avoid becoming pregnant while
taking IMBRUVICA®. If this drug is used during pregnancy
or if the patient becomes pregnant while taking this drug, the
patient should be apprised of the potential hazard to a fetus.
ADVERSE REACTIONS
The most common adverse reactions (≥25%) in patients with B-cell
malignancies (MCL, CLL, WM) were thrombocytopenia, neutropenia,
diarrhea, anemia, fatigue, musculoskeletal pain, bruising, nausea,
upper respiratory tract infection, and rash. Seven percent of
patients receiving IMBRUVICA® discontinued treatment due
to adverse events.
DRUG INTERACTIONS
CYP3A Inhibitors - Avoid co-administration with strong
and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must
be used, reduce the IMBRUVICA® dose.
CYP3A Inducers - Avoid co-administration with strong
CYP3A inducers.
SPECIFIC POPULATIONS
Hepatic Impairment - Avoid use in patients with moderate
or severe baseline hepatic impairment. In patients with mild
impairment, reduce IMBRUVICA® dose.
For additional important safety information, please see Full
Prescribing Information
at http://www.imbruvica.com/downloads/Prescribing_Information.pdf.
About Pharmacyclics
Pharmacyclics, Inc. (NASDAQ: PCYC)
is a biopharmaceutical company focused on developing and
commercializing innovative small-molecule drugs for the treatment
of cancer and immune mediated diseases. The company's mission is to
build a viable biopharmaceutical company that designs, develops and
commercializes novel therapies intended to improve quality of life,
increase duration of life and resolve serious unmet medical needs.
It will do so by identifying and controlling promising product
candidates based on scientific development and administrative
expertise, developing its products in a rapid, cost-efficient
manner and, pursuing commercialization and/or development partners
when and where appropriate.
Pharmacyclics markets IMBRUVICA and has three product candidates
in clinical development and several preclinical molecules in lead
optimization. The company is committed to high standards of ethics,
scientific rigor and operational efficiency as it moves each of
these programs to commercialization. Pharmacyclics is headquartered
in Sunnyvale, CA. To learn more,
please visit www.pharmacyclics.com.
NOTE: This announcement may contain forward-looking
statements made in reliance upon the safe harbor provisions of
Section 27A of the Securities Act of 1933, as amended, and Section
21E of the Securities Exchange Act of 1934, as amended, including
statements, among others, relating to our future capital
requirements, including our expected liquidity position and timing
of the receipt of certain milestone payments, and the sufficiency
of our current assets to meet these requirements, our future
results of operations, our expectations for and timing of ongoing
or future clinical trials and regulatory approvals for any of our
product candidates, and our plans, objectives, expectations and
intentions. Because these statements apply to future events, they
are subject to risks and uncertainties. When used in this
announcement, the words "anticipate", "believe", "estimate",
"expect", "expectation", "goal", "should", "would", "project",
"plan", "predict", "intend", "target" and similar expressions are
intended to identify such forward-looking statements. These
forward-looking statements are based on information currently
available to us and are subject to a number of risks, uncertainties
and other factors that could cause our actual results, performance,
expected liquidity or achievements to differ materially from those
projected in, or implied by, these forward-looking statements.
Factors that may cause such a difference include, without
limitation, our need for substantial additional financing and the
availability and terms of any such financing, the safety and/or
efficacy results of clinical trials of our product candidates, our
failure to obtain regulatory approvals or comply with ongoing
governmental regulation, our ability to commercialize, manufacture
and achieve market acceptance of any of our product candidates, for
which we rely heavily on collaboration with third parties, and our
ability to protect and enforce our intellectual property rights and
to operate without infringing upon the proprietary rights of third
parties. Although we believe that the expectations reflected in the
forward-looking statements are reasonable, we cannot guarantee
future results, performance or achievements and no assurance can be
given that the actual results will be consistent with these
forward-looking statements. For more information about the risks
and uncertainties that may affect our results, please see the Risk
Factors section of our filings with the Securities and Exchange
Commission, including our Form 10-K for the year ended December 31, 2013 and quarterly reports on Form
10-Q. We do not intend to update any of the forward-looking
statements after the date of this announcement to conform these
statements to actual results, to changes in management's
expectations or otherwise, except as may be required by law.
IMBRUVICA is a registered trademark of Pharmacyclics, Inc.
1 Stedman's Online. Xenograft. Available at:
http://stedmansonline.com/content.aspx?id=mlrX0500000101&termtype=t.
Accessed April 2015.
2 Pancreatic Cancer U.K. Types of pancreatic cancer.
Available at: http://www.pancreaticcancer.org.uk/types. Accessed
April 2015.
3 National Cancer Institute. Scientific Framework for
Pancreatic Ductal Adenocarcinoma (PDAC). Available at:
http://deainfo.nci.nih.gov/advisory/ctac/workgroup/pc/pdacframework.pdf.
Accessed April 2015.
4 IMBRUVICA Prescribing Information, January
2015
5 Genetics Home Reference. Isolated growth hormone
deficiency. Available at:
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed April 2015.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/ibrutinib-imbruvica-improves-outcomes-for-pancreatic-ductal-adenocarcinoma-in-mouse-models-300068264.html
SOURCE Pharmacyclics, Inc.