NORTH CHICAGO, Ill.,
Jan. 18, 2019 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced an update on the Phase 3
RESOLVE trial (PCYC-1137) of ibrutinib (IMBRUVICA®) in
combination with chemotherapy agents nab-paclitaxel and gemcitabine
versus placebo in combination with these chemotherapy agents in
patients with metastatic pancreatic adenocarcinoma
(cancer). Metastatic pancreatic cancer is an aggressive and
difficult-to-treat solid tumor primarily treated with chemotherapy
today. IMBRUVICA is a first-in-class Bruton's tyrosine kinase (BTK)
inhibitor jointly developed and commercialized by Pharmacyclics
LLC, an AbbVie company, and Janssen Biotech, Inc. (Janssen).
IMBRUVICA has been available in the U.S. since 2013 and is
FDA-approved for use in five B-cell
blood cancers, as well as in chronic graft-versus-host-disease for
a total of nine FDA-approved indications.
PCYC-1137 evaluated the efficacy of ibrutinib in combination
with nab-paclitaxel and gemcitabine for the first-line treatment of
patients with metastatic pancreatic cancer. Patients were
randomized 1:1 to receive ibrutinib and nab-paclitaxel and
gemcitabine combination treatment arm (n=211 study patients) versus
the placebo and nab-paclitaxel and gemcitabine combination
treatment arm (n=213 study patients). At conclusion, the study did
not meet its primary endpoint of improving progression-free
survival (PFS) or overall survival (OS) benefit among the study population. Safety
data collected from the study were consistent with the existing
safety information for the study therapies. The full results from
this trial will be submitted for publication to a future scientific
conference and/or a peer-reviewed medical journal.
"We continue to evaluate the potential of IMBRUVICA as a cancer
treatment alone or in combination for a variety of cancer types. We
are passionately advancing our robust ibrutinib scientific
development program to continue to advance cancer standards of
care, particularly in areas that have unmet medical need," said
Danelle James, M.D., M.A.S., Head of
Clinical Science at Pharmacyclics LLC, an AbbVie company.
About the IMBRUVICA (ibrutinib) Clinical Program
IMBRUVICA has a robust clinical oncology development program
with more than 130 ongoing clinical trials. IMBRUVICA is being
studied alone and in combination with other treatments in several
blood and solid tumor cancers and other serious illnesses. There
are approximately 30 ongoing company-sponsored trials, 14 of which
are in Phase 3, and more than 100 investigator-sponsored trials and
external collaborations that are active around the world. To date,
more than 135,000 patients around the world have been treated with
IMBRUVICA in clinical practice and clinical trials.
About the RESOLVE Study (PCYC-1137)
PCYC-1137 is a Pharmacyclics, an AbbVie company, sponsored
randomized, multicenter, double-blind, placebo-controlled, Phase 3
study of the Bruton's tyrosine kinase (BTK) inhibitor
ibrutinib in combination with nab-paclitaxel and gemcitabine versus
placebo in combination with nab-paclitaxel and gemcitabine, in the
first-line treatment of patients with metastatic pancreatic
adenocarcinoma.
About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily
therapy that mainly works by blocking a protein called Bruton's
tyrosine kinase (BTK). 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 as well as other
serious, debilitating conditions.2 IMBRUVICA blocks
signals that tell malignant B cells to multiply and spread
uncontrollably.
- IMBRUVICA was first approved for adult patients with mantle
cell lymphoma (MCL) who have received at least one prior therapy in
November 2013.
- Soon after, IMBRUVICA was initially approved in adult chronic
lymphocytic leukemia (CLL) patients who have received at least one
prior therapy in February 2014. By
July 2014, the therapy received
approval for adult CLL patients with 17p deletion, and by
March 2016, the therapy was approved
as a frontline CLL treatment.
- IMBRUVICA was approved for adult patients with Waldenström's
Macroglobulinemia (WM) in January
2015.
- In May 2016, IMBRUVICA was
approved in combination with bendamustine and rituximab (BR) for
adult patients with CLL/ small lymphocytic lymphoma (SLL).
- In January 2017, IMBRUVICA was
approved for adult patients with marginal zone lymphoma (MZL) who
require systemic therapy and have received at least one prior
anti-CD20-based therapy.
- In August 2017, IMBRUVICA was
approved for adult patients with chronic graft versus host disease
(cGVHD) that failed to respond to one or more lines of systemic
therapy.
- In August 2018, IMBRUVICA plus
rituximab was approved for adult patients with WM.
Accelerated approval was granted for the MCL and MZL indications
based on overall response rate. Continued approval for MCL and MZL
may be contingent upon verification and description of clinical
benefit in confirmatory trials.
IMBRUVICA has been granted four Breakthrough Therapy
Designations from the U.S. FDA. This designation is intended to
expedite the development and review of a potential new drug for
serious or life-threatening diseases.3 IMBRUVICA
was one of the first medicines to receive FDA approval via the new
Breakthrough Therapy Designation pathway.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Grade 3 or higher
bleeding events (intracranial hemorrhage [including subdural
hematoma], gastrointestinal bleeding, hematuria, and
post-procedural hemorrhage) have occurred in 3% of patients, with
fatalities occurring in 0.3% of 1,011 patients exposed to
IMBRUVICA® in clinical trials. Bleeding events of any
grade, including bruising and petechiae, occurred in 44% 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 and
patients should be monitored for signs of bleeding.
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 (including
bacterial, viral, or fungal) have occurred with
IMBRUVICA® therapy. Grade 3 or greater infections
occurred in 24% of 1,011 patients exposed to IMBRUVICA®
in clinical trials. Cases of progressive multifocal
leukoencephalopathy (PML) and Pneumocystis jirovecii
pneumonia (PJP) have occurred in patients treated with
IMBRUVICA®. Consider prophylaxis according to standard
of care in patients who are at increased risk for opportunistic
infections.
Monitor and evaluate patients for fever and infections and treat
appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias
including neutropenia (23%), thrombocytopenia (8%), and anemia (3%)
based on laboratory measurements occurred in patients with B-cell
malignancies treated with single agent IMBRUVICA®.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac
arrhythmias have occurred with IMBRUVICA® therapy. Grade
3 or greater ventricular tachyarrhythmias occurred in 0.2% of
patients, and Grade 3 or greater atrial fibrillation and atrial
flutter occurred in 4% of 1,011 patients exposed to
IMBRUVICA® in clinical trials. These events have
occurred particularly in patients with cardiac risk factors,
hypertension, acute infections, and a previous history of cardiac
arrhythmias.
Periodically monitor patients clinically for cardiac
arrhythmias. Obtain an ECG for patients who develop arrhythmic
symptoms (e.g., palpitations, lightheadedness, syncope, chest pain)
or new onset dyspnea. Manage cardiac arrhythmias appropriately, and
if it persists, consider the risks and benefits of
IMBRUVICA® treatment and follow dose modification
guidelines.
Hypertension: Hypertension has occurred in 12% of 1,011
patients treated with IMBRUVICA® in clinical trials with
a median time to onset of 5 months (range, 0.03 to 22 months).
Monitor patients for new onset hypertension or hypertension that is
not adequately controlled after starting IMBRUVICA®.
Adjust existing anti-hypertensive medications and/or initiate
anti-hypertensive treatment as appropriate.
Second Primary Malignancies: Other malignancies (9%)
including non-skin carcinomas (2%) have occurred in 1,011 patients
treated with IMBRUVICA® in clinical trials. The
most frequent second primary malignancy was non-melanoma skin
cancer (6%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been
infrequently reported with IMBRUVICA® therapy. Assess
the baseline risk (e.g., high tumor burden) and take appropriate
precautions.
Monitor patients closely and treat as appropriate.
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® and for 1 month after cessation
of therapy. 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. Advise men to avoid
fathering a child during the same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse
reactions (≥20%) in patients with B-cell malignancies (MCL,
CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, neutropenia
(58%)*, diarrhea (42%), anemia (39%)*, rash (31%), musculoskeletal
pain (31%), bruising (31%), nausea (28%), fatigue (27%), hemorrhage
(23%), and pyrexia (20%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients
with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were
neutropenia (36%)*, thrombocytopenia (15%)*, and pneumonia
(10%).
Approximately 6% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of
patients had a dose reduction due to adverse reactions.
Approximately 4%-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL
[13%]) of patients discontinued due to adverse reactions.
cGVHD: The most common adverse reactions (≥20%) in
patients with cGVHD were fatigue (57%), bruising (40%), diarrhea
(36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms
(29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia
(21%).
The most common Grade 3 or 4 adverse reactions (≥5%) reported in
patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia
(10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache
(5%), musculoskeletal pain (5%), and pyrexia (5%).
Twenty-four percent of patients receiving
IMBRUVICA® in the cGVHD trial discontinued
treatment due to adverse reactions. Adverse reactions leading to
dose reduction occurred in 26% of patients.
*Treatment-emergent decreases (all grades) were based on
laboratory measurements and adverse reactions.
DRUG INTERACTIONS
CYP3A Inhibitors: Dose adjustments may be
recommended.
CYP3A Inducers: Avoid coadministration with strong CYP3A
inducers.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid
use of IMBRUVICA® in patients with severe baseline
hepatic impairment. In patients with mild or moderate impairment,
reduce IMBRUVICA® dose.
Please click here for full Prescribing
Information.
About AbbVie
AbbVie is a global, research and development-based
biopharmaceutical company committed to developing innovative
advanced therapies for some of the world's most complex and
critical conditions. The company's mission is to use its expertise,
dedicated people and unique approach to innovation to markedly
improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie on
Twitter, Facebook, LinkedIn or Instagram.
Forward-Looking Statements
Some statements in this news release are, or may be considered,
forward-looking statements for purposes of the Private Securities
Litigation Reform Act of 1995. The words "believe," "expect,"
"anticipate," "project" and similar expressions, among others,
generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially
from those indicated in the forward-looking statements. Such risks
and uncertainties include, but are not limited to, challenges to
intellectual property, competition from other products,
difficulties inherent in the research and development process,
adverse litigation or government action, and changes to laws and
regulations applicable to our industry. Additional information
about the economic, competitive, governmental, technological and
other factors that may affect AbbVie's operations is set forth in
Item 1A, "Risk Factors," of AbbVie's 2017 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. AbbVie undertakes no obligation to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
IMBRUVICA is a registered trademark of Pharmacyclics LLC.
1 Cancer Network. Treatment of Metastatic
Pancreatic Adenocarcinoma: A Review.
http://www.cancernetwork.com/oncology-journal/treatment-metastatic-pancreatic-adenocarcinoma-review.
Accessed January 2019.
2 Genetics Home Reference. Isolated growth
hormone deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed
January 2019.
3 U.S. Food and Drug Administration. Fact Sheet:
Breakthrough Therapies.
https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed
January 2019.
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SOURCE AbbVie