NORTH CHICAGO, Ill.,
Jan. 19, 2017 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a global biopharmaceutical company, today announced
the U.S. Food and Drug Administration (FDA) approved IMBRUVICA®
(ibrutinib) for the treatment of patients with relapsed/refractory
(R/R) marginal zone lymphoma (MZL) who require systemic therapy and
have received at least one prior anti-CD20-based
therapy.1 This indication is approved under
accelerated approval based on overall response rate (ORR), and
continued approval may be contingent upon verification and
description of clinical benefit in a confirmatory trial. IMBRUVICA
is jointly developed and commercialized by Pharmacyclics LLC, an
AbbVie company, and Janssen Biotech, Inc.
"The FDA approval of IMBRUVICA for
relapsed/refractory marginal zone lymphoma is significant, and
we are proud of the culmination of this extensive clinical research
program, representing the first approved treatment specifically for
patients with this rare type of non-Hodgkin's lymphoma," said
Darrin Beaupre, M.D., Ph.D., Head of
Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie
company. "This milestone marks the fifth patient population for
whom IMBRUVICA is now approved and broadens the number of patients
who may be treated with the medication. We continue to research
IMBRUVICA across many disease areas, including but not limited to
other B-cell malignancies."
The approval in MZL is based on data from the Phase 2,
open-label, multi-center, single-arm PCYC-1121 study, which
evaluated the safety and efficacy of IMBRUVICA in MZL patients who
require systemic therapy and have received at least one prior
anti-CD20-based therapy. The efficacy analysis included 63 patients
with three sub-types of MZL: mucosa-associated lymphoid tissue
(MALT; N=32), nodal (N=17) and splenic (N=14). The ORR was achieved
in nearly half (46%) of the patients (95% CI: 33.4-59.1) as
assessed by an Independent Review Committee (IRC) using
criteria adopted from the International Working Group criteria for
malignant lymphoma, with efficacy observed across all three MZL
sub-types. The median time to response was 4.5 months (range,
2.3-16.4 months). In the trial, 3.2% of patients had a
complete response (CR) and 42.9% of patients had a partial response
(PR). The median duration of responses was not reached (NR) (range
16.7 months to NR).1 The data were previously presented
at the American Society of Hematology (ASH) Annual Meeting
(December 2016).
"In the Phase 2 trial, IMBRUVICA demonstrated impressive response
rates and duration of response in relapsed/refractory marginal zone
lymphoma patients," said Ariela Noy,
M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer
Center in New York and lead
investigator of the study.* "The hematology-oncology community
welcomes a new option like IMBRUVICA, which helps fill a
significant treatment gap for previously treated MZL patients who
are in need of non-chemotherapy options."
Overall, the safety data from this study was consistent with the
known safety profile of IMBRUVICA in B-cell malignancies. The most
common adverse events (AEs) of all Grades (occurring in ≥20% of MZL
patients treated with IMBRUVICA) included thrombocytopenia (49%),
fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%),
musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea
(25%), peripheral edema and arthralgia (24% each), neutropenia and
cough (22% each), and dyspnea and upper respiratory tract infection
(21% each). The most common (>10%) Grade 3 or 4 AEs were
decreases in hemoglobin and neutrophils (13% each) and pneumonia
(10%).1
The risks associated with IMBRUVICA as listed in the Warnings
and Precautions section of the prescribing information
are hemorrhage, infections, cytopenias, atrial fibrillation,
hypertension, secondary primary malignancies, tumor lysis syndrome
and embryo fetal toxicities.
IMBRUVICA is now approved to treat patients with MZL who require
systemic therapy and have received at least one prior
anti-CD20-based therapy, as well as patients with other
non-Hodgkin's lymphomas, including 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).1 Continued
approval for the MZL and MCL indications may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
About the Study
The Phase 2 PCYC-1121 trial is a
Pharmacyclics-sponsored study that 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.2
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.3
MZL accounts for approximately 8% of all cases of non-Hodgkin's
lymphoma in adults, and the median age of diagnosis is 65 years
old.3,4 There are three sub-types of MZL:
mucosa-associated lymphoid tissue, nodal and
splenic.3
About IMBRUVICA
IMBRUVICA (ibrutinib) 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.1,5 IMBRUVICA blocks signals that tell malignant B
cells to multiply and spread uncontrollably.1
IMBRUVICA is FDA-approved in five distinct patient populations:
CLL, SLL, WM, along with previously-treated MCL and
MZL.1
- IMBRUVICA was first approved for patients with MCL who have
received at least one prior therapy in November 2013.
- Soon after, IMBRUVICA was initially approved in CLL patients
who have received at least one prior therapy in February 2014. By July
2014, the therapy received approval for CLL patients with
17p deletion, and by March 2016, the
therapy was approved as a frontline CLL treatment.
- IMBRUVICA was approved for patients with WM in January 2015.
- In May 2016, IMBRUVICA was
approved in combination with bendamustine and rituximab (BR) for
patients with previously treated CLL/SLL.
- In January 2017, IMBRUVICA was
approved for patients with MZL who require systemic therapy and
have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indication
based on overall response rate. Continued approval for MCL and MZL
may be contingent upon verification and description of
clinical benefit in confirmatory trials.1
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 company-sponsored trials underway, 14 of which are
Phase 3. In addition, there are approximately 100
investigator-sponsored trials and external collaborations that are
ongoing and active 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) and Pneumocystis jirovecii
pneumonia (PJP) 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, 13% to 29%), thrombocytopenia (range,
5% to 17%), and anemia (range, 0% to 13%) 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,
3% 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, 2%
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. Advise men to avoid fathering a child during the
same time period.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) in patients with B-cell
malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia** (61%),
thrombocytopenia** (62%), diarrhea (43%), anemia** (41%),
musculoskeletal pain (30%), rash (30%), nausea (29%), bruising
(30%), fatigue (29%), hemorrhage (22%), 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%). The most common Grade 3 or 4 non-hematologic
adverse reactions (≥5%) in MZL patients were pneumonia (10%),
fatigue (6%), diarrhea (5%), rash (5%), and hypertension (5%).
Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of
patients had a dose reduction due to adverse reactions.
Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL
[13%]) of patients discontinued due to adverse reactions. Most
common adverse reactions leading to discontinuation were pneumonia,
hemorrhage, atrial fibrillation, rash, and neutropenia (1% each) in
CLL/SLL patients and subdural hematoma (1.8%) in MCL patients. The
most common adverse reactions leading to discontinuation were
interstitial lung disease, diarrhea, and rash (1.6% each) in WM and
MZL 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.
PRC-02580 1/17
1 IMBRUVICA US Prescribing Information, January
2017.
2 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.
3 Lymphoma Research Foundation. "Marginal Zone
Lymphoma." Available from:
http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6554677.
Accessed January 2017.
4 Lymphoma Research Foundation. "Getting the Facts:
Marginal Zone Lymphoma." Available from:
http://www.lymphoma.org/atf/cf/%7baaf3b4e5-2c43-404c-afe5-fd903c87b254%7d/lrf_factsheet_marginal_zone_lymphoma.pdf.
Accessed January 2017.
5 Genetics Home Reference. Isolated growth hormone
deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed January 2017.
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