NORTH CHICAGO, Ill.,
Dec. 5, 2016 /PRNewswire/
-- AbbVie (NYSE: ABBV), a global biopharmaceutical company,
today announced efficacy and safety findings from a Phase 2 study
demonstrating that nearly half (48%) of patients with
relapsed/refractory (R/R) marginal zone lymphoma (MZL) had a
complete or partial response with single-agent ibrutinib
(IMBRUVICA®), as assessed by Independent Review
Committee (IRC) investigators. The median duration of response was
not reached.1 These data will be presented today in an
oral presentation at the 58th American Society of
Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (abstract #1213). IMBRUVICA, a
first-in-class Bruton's tyrosine kinase (BTK) inhibitor, is jointly
developed and commercialized by Pharmacyclics LLC, an AbbVie
company, and Janssen Biotech, Inc.
MZL is a diverse group of slow-growing non-Hodgkin's lymphomas
arising from white blood cells (lymphocytes) at the edges of
lymphoid tissue.2 MZL accounts for approximately 12% of
all cases of non-Hodgkin's lymphoma in adults and the median age at
diagnosis is 65 years old.3 There are currently no
approved treatments or standards of care specifically indicated for
patients with MZL in the United
States.
"We are pleased with the 48% response rate seen with ibrutinib
in this trial, as the hematology-oncology community has a need for
effective new therapies to treat marginal zone lymphoma," said
Ariela Noy, M.D., Hematologic
Oncologist at Memorial Sloan Kettering Cancer Center in
New York and lead investigator of
the study.* "In particular, a non-chemotherapy targeted oral option
like ibrutinib could represent an important step forward for
patients with MZL to keep this incurable type of cancer under
control."
In this multicenter, open-label trial, 63 MZL patients
(including splenic MZL [SMZL], nodal MZL [NMZL] and extranodal MZL
[EMZL] subtypes) received one or more prior therapies including at
least one CD20-directed regimen (chemo-immunotherapy or rituximab
monotherapy). In the study, 79% of patients experienced some
tumor reduction (50 out of 63 patients) and overall response rates
(ORR) was 48%, implying that BTK signaling is an important growth
and survival factor in MZL. The median time to initial response was
4.5 months.1
Overall, the safety data from this study was consistent with the
known safety profile of ibrutinib in B-cell malignancies. The most
common adverse events (AEs) included fatigue (44%), diarrhea (43%),
anemia (33%), nausea (25%), thrombocytopenia, peripheral edema and
arthralgia (24% each), cough (22%), dyspnea and URTI (21% each).
Grade 3 or 4 AEs occurred in 63% of patients. The most frequent
were anemia (14%), pneumonia (8%) and fatigue (6%). Grade 1 and 2
atrial fibrillation occurred in four (6%) patients.1
"These findings contribute to the growing body of evidence
exploring the use of ibrutinib in different types of hematologic
cancers, including marginal zone lymphoma and its three sub-types,"
said Darrin Beaupre, M.D., Ph.D.,
Head of Early Development and Immunotherapy at Pharmacyclics LLC,
an AbbVie company. "Results from this study support the recent
submission of a supplemental New Drug Application to include more
patients who may benefit from treatment with ibrutinib."
About the Study
The Phase 2 study evaluated the
safety and efficacy of ibrutinib in patients with R/R MZL. The
primary objective of the trial was ORR as assessed by an IRC.
Duration of response (DOR), progression-free survival (PFS),
overall survival (OS) and safety were secondary
objectives.1 Data from this study were submitted to the
U.S. Food and Drug Administration (FDA) in September 2016 as
part of a supplemental New Drug Application (sNDA) to expand the
current indication for IMBRUVICA.
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.4,5 IMBRUVICA blocks signals that tell
malignant B cells to multiply and spread
uncontrollably.4
IMBRUVICA is approved to treat patients with CLL/SLL including
patients with 17p deletion, patients with mantle cell lymphoma who
have received at least one prior therapy and patients with
Waldenström's macroglobulinemia. 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.4
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. IMBRUVICA has one of the most robust clinical
oncology development programs for a single molecule in the industry
with nearly 30 (n=27) company-sponsored trials underway, 14 of
which are Phase 3. In addition, there are more than 40 (n=44)
investigator-sponsored trials taking place around the
world. To date, more than 65,000 patients around the world
have been treated with IMBRUVICA in clinical practice and clinical
trials.
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/prescribing-information
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.
*Disclaimer: Dr. Noy served as an investigator of this
Pharmacyclics-sponsored clinical study. Dr. Noy does not have a
financial interest in the company.
1 Noy, A, et al. Single-Agent Ibrutinib Demonstrates
Efficacy and Safety in Patients with Relapsed/Refractory Marginal
Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. ASH 2016.
Abstract #1213.
2 El-Zimaity, H. "Marginal zone B-cell lymphoma."
Available from:
http://emedicine.medscape.com/article/1610599-overview#showall.
Accessed November 2016.
3 Lymphoma Research Foundation. "Marginal zone
lymphoma." Available from:
http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6554677.
Accessed November 2016.
4 IMBRUVICA US Prescribing Information, June
2016.
5 Genetics Home Reference. Isolated growth hormone
deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed
November 2016.
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