NORTH CHICAGO, Ill.,
Sept. 26, 2016 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a global biopharmaceutical company, today announced
that it submitted a supplemental New Drug Application (sNDA) to the
U.S. Food and Drug Administration (FDA) for ibrutinib
(IMBRUVICA®) to treat patients with marginal zone
lymphoma (MZL). MZL is a slow-growing form of non-Hodgkin's
lymphoma. The Company's sNDA submission is based on data from a
multi-center, open-label Phase II PCYC-1121-CA trial assessing
ibrutinib as a single-agent treatment for MZL. If approved, MZL
will be the fifth unique type of blood cancer indication for
IMBRUVICA. IMBRUVICA is jointly developed and commercialized by
Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc.
"We continue to explore the use of ibrutinib in non-Hodgkin's
lymphoma, including marginal zone lymphoma and its three sub-types,
given its unique mechanism of action and ability to target the
B-cell receptor pathway," said Darrin
Beaupre, M.D., Ph.D., Head of Early Development and
Immunotherapy at Pharmacyclics. "MZL in its advanced stages is
currently an incurable form of hematologic cancer and new treatment
options are needed. We look forward to working with the FDA and our
partners at Janssen to bring this promising treatment to patients
with MZL."
The Phase II PCYC-1121-CA trial is a Pharmacyclics-sponsored
study that enrolled 63 previously treated patients with MZL,
including splenic MZL (SMZL), nodal MZL (NMZL) and extranodal MZL
(EMZL), in the U.S., EU and other regions. Patients received
monotherapy ibrutinib orally, once daily until progression or
unacceptable toxicity. The primary endpoint of the study was
overall response rate as assessed by an Independent Review
Committee. A key secondary endpoint was safety.
These clinical data have been submitted for publication in a
peer-reviewed journal and presentation at an upcoming medical
conference. More information about the study can be found on
www.clinicaltrials.gov.
IMBRUVICA is currently approved to treat patients with chronic
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),
including patients with 17p deletion, patients with mantle cell
lymphoma (MCL) who have received at least one prior therapy and
patients with Waldenström's macroglobulinemia (WM).
About Marginal Zone Lymphoma
Marginal zone lymphoma
(MZL) is a slow-growing B-cell lymphoma arising from white blood
cells (lymphocytes) at the edges of lymphoid tissue.1
MZL accounts for approximately 12 percent of all cases of
non-Hodgkin's lymphoma in adults, and the median age of diagnosis
is 65 years old.2 There are currently no approved
treatments or standards of care specifically indicated for patients
with MZL.2
About IMBRUVICA
IMBRUVICA is a first-in-class,
oral, once-daily therapy that inhibits 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.3,4
IMBRUVICA blocks signals that tell malignant B cells to multiply
and spread uncontrollably.3
IMBRUVICA is approved to treat patients with CLL/SLL including
patients with 17p deletion, patients with MCL who have received at
least one prior therapy and patients with WM. Accelerated approval
was granted for the MCL indication based on overall response rate.
Continued approval for this indication may be contingent upon
verification of clinical benefit in confirmatory
trials.3
IMBRUVICA was one of the first medicines to receive U.S. FDA
approval via the new Breakthrough Therapy Designation pathway.
IMBRUVICA is being studied alone and in combination with other
treatments in several blood and solid tumor cancers and other
serious illnesses. More than 6,000 patients have been treated with
IMBRUVICA in clinical trials. Currently, 14 Phase 3 trials have
been initiated with IMBRUVICA and more than 90 trials are
registered on www.clinicaltrials.gov.
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 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 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 postsurgery depending upon the type of surgery and the risk of
bleeding.
Infections - Fatal and nonfatal infections have occurred
with IMBRUVICA® therapy. Grade 3 or greater
infections occurred in 14% to 29% of patients. Cases of progressive
multifocal leukoencephalopathy (PML) have occurred in patients
treated with IMBRUVICA®. Evaluate patients
for fever and infections and treat appropriately.
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%) based on laboratory
measurements occurred in patients treated with single agent
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, hypertension, acute infections, and a
previous history of atrial fibrillation. Periodically monitor
patients clinically for atrial fibrillation. Patients who develop
arrhythmic symptoms (eg, palpitations, lightheadedness) or
new-onset dyspnea should have an ECG performed. Atrial fibrillation
should be managed appropriately and if it persists, consider the
risks and benefits of IMBRUVICA® treatment
and follow dose modification guidelines.
Hypertension - Hypertension (range, 6% to 17%) has
occurred in patients treated with IMBRUVICA® with a
median time to onset of 4.6 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 antihypertensive medications and/or initiate
antihypertensive treatment as appropriate.
Second Primary Malignancies - Other malignancies (range,
5% to 16%) including non-skin carcinomas (range, 1% to 4%) have
occurred in patients treated with
IMBRUVICA®. The most frequent second
primary malignancy was non-melanoma skin cancer (range, 4% to
13%).
Tumor Lysis Syndrome - Tumor lysis syndrome has been
infrequently reported with IMBRUVICA®
therapy. Assess the baseline risk (eg, 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.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) in patients with B-cell
malignancies (MCL, CLL/SLL, and WM) were neutropenia* (64%),
thrombocytopenia* (63%), diarrhea (43%), anemia* (41%),
musculoskeletal pain (30%), rash (29%), nausea (29%), bruising
(29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).
*Based on adverse reactions and/or laboratory measurements
(noted as platelets, neutrophils, or hemoglobin decreased).
The most common Grade 3 or 4 non-hematologic adverse reactions
(≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%),
atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin
infections (5%). Approximately 6% (CLL), 14% (MCL), and 11% (WM) of
patients had a dose reduction due to adverse reactions.
Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients
discontinued due to adverse reactions. Most frequent adverse
reactions leading to discontinuation were pneumonia, hemorrhage,
atrial fibrillation, rash and neutropenia (1% each) in CLL patients
and subdural hematoma (1.8%) in MCL patients.
DRUG INTERACTIONS
CYP3A Inhibitors - Avoid coadministration with strong and
moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be
used, reduce the IMBRUVICA® dose.
CYP3A Inducers - Avoid coadministration 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.
Please see Full Prescribing Information:
https://www.imbruvica.com/docs/librariesprovider7/default-document-library/prescribing_information.pdf.
About AbbVie
AbbVie is a global, research-based
biopharmaceutical company formed in 2013 following separation from
Abbott Laboratories. The company's mission is to use its expertise,
dedicated people and unique approach to innovation to develop and
market advanced therapies that address some of the world's most
complex and serious diseases. Together with its wholly-owned
subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people
worldwide and markets medicines in more than 170 countries. For
further information on the company and its people, portfolio and
commitments, please visit www.abbvie.com. Follow @abbvie on Twitter
or view careers on our Facebook or LinkedIn page.
Forward-Looking Statements
Some statements in this
news release may be 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," in
AbbVie's 2015 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 El-Zimaity, H. "Marginal Zone B-cell Lymphoma."
Available from:
http://emedicine.medscape.com/article/1610599-overview#showall.
Accessed August 2016.
2 Lymphoma Research Foundation. "Marginal Zone
Lymphoma." Available from:
http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6554677.
Accessed August 2016.
3 IMBRUVICA US Prescribing Information, May
2016.
4 Genetics Home Reference. Isolated growth hormone
deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed August 2016.
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SOURCE AbbVie Inc.