NORTH CHICAGO, Ill.,
Dec. 7, 2019 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced results from an extended
follow-up analysis of the Phase 3 E1912 clinical study – designed
and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN)
and sponsored by the National Cancer Institute (NCI), which is part
of the National Institutes of Health. Study results showed superior
progression-free survival (PFS) and overall survival (OS) in
patients with chronic lymphocytic leukemia (CLL) new to
treatment.
These results demonstrated the benefits of IMBRUVICA®
(ibrutinib) plus rituximab compared to a standard
chemoimmunotherapy regimen of fludarabine, cyclophosphamide and
rituximab (FCR) for previously untreated patients with CLL aged 70
years or younger. These results were featured today in the CLL
Therapy Oral Presentation Session at the American Society of
Hematology (ASH) Annual Meeting, and served as the basis of the
recent supplemental New Drug Application (sNDA) to the U.S. Food
and Drug Administration (FDA) to expand further the IMBRUVICA
prescribing label in CLL.
Additionally, a new integrated analysis of up to six years of
long-term follow-up from the Phase 3 RESONATE™ and
RESONATE-2 studies will be presented on December 8 at the ASH Annual Meeting, evaluating
the use of IMBRUVICA monotherapy in previously untreated patients.
Results showed better PFS, OS and overall response rate (ORR), with
good tolerability compared to use in the relapsed/refractory (R/R)
setting.
"These latest findings add to the extensive clinical evidence
supporting the use of IMBRUVICA, the most comprehensively studied
BTK inhibitor in CLL, as both a single-agent and as a combination
regimen to improve patient outcomes in early lines of treatment,
which has previously been reserved for chemoimmunotherapy," said
Danelle James, M.D., M.A.S.,
IMBRUVICA Clinical Development Lead, Pharmacyclics LLC, an AbbVie
company. "We're pleased to present extended follow-up results from
the Phase 3 E1912 and RESONATE/RESONATE-2 studies at this year's
ASH Annual Meeting – all of which are landmark clinical trials that
have uniquely changed our understanding of CLL."
"Phase 3 RESONATE and RESONATE-2 trials have proven to be
cornerstone studies that have significantly advanced the treatment
of CLL among a variety of patients – and the latest data presented
at this year's ASH Annual Meeting demonstrate using IMBRUVICA alone
and earlier in CLL treatment results in improved patient outcomes,"
said Paul M. Barr, M.D., study
investigator of the Phase 3 RESONATE and RESONATE-2 trials, and
Associate Professor of Medicine, Hematology/Oncology at the Wilmot
Cancer Institute, University of
Rochester Medical Center, Rochester, New York. "These results reaffirm
the sustained disease control and safety profile of IMBRUVICA and
further support its use as a chemotherapy-free option for
previously untreated patients living with this common form of adult
leukemia."
IMBRUVICA is a once-daily, first-in-class Bruton's tyrosine
kinase (BTK) inhibitor that is administered orally, and is jointly
developed and commercialized by Pharmacyclics LLC, an AbbVie
company, and Janssen Biotech, Inc.
Abstract #33: E1912 extended follow-up of IMBRUVICA plus
rituximab compared to FCR in patients with CLL/SLL aged 70 or
younger
Oral Presentation: Saturday, December
7, 2019 at 7:30 a.m.
EST
Longer-term outcomes data from the Phase 3 E1912 clinical trial
– designed and conducted by ECOG-ACRIN and sponsored by the NCI –
were presented today in an oral session. As previously reported in
earlier data readouts, the study evaluated 354 previously untreated
patients with CLL aged 70 years or younger who were randomly
assigned to receive IMBRUVICA and rituximab or six courses of
intravenous FCR chemoimmunotherapy every 28 days. The study met the
primary endpoints of PFS and OS.
At a median follow-up of 48 months, 73 percent of patients in
the IMBRUVICA plus rituximab treatment arm remained on IMBRUVICA
with median time on treatment of 43 months (range of 0.2 to 61
months). The median time to progression or death after
discontinuing IMBRUVICA was 23 months. Superior PFS benefits were
sustained for the IMBRUVICA plus rituximab arm compared to the FCR
treatment arm (hazard ratio [HR]: 0.39; 95 percent confidence
interval [CI], 0.26-0.57; p<0.0001). OS also continued to favor
the IMBRUVICA plus rituximab arm (HR=0.34, 95 percent CI,
0.15-0.79; p=0.009). Grade 3 and above treatment-related adverse
events (AEs) were observed in 70 percent of patients in the
IMBRUVICA plus rituximab arm versus 80 percent in the FCR arm (odds
ratio [OR]: 0.56; 95 percent CI, 0.34 – 0.90; p=0.013).
The E1912 study served as the basis of the recent sNDA to the
U.S. FDA to expand the IMBRUVICA label to include the combination
with rituximab for the first-line treatment of patients with CLL or
SLL. The submission is being reviewed by the FDA under the
Real-Time Oncology Review pilot program.
Abstract #3054: New RESONATE/RESONATE-2
long-term analysis of ibrutinib monotherapy in earlier lines of CLL
treatment
Poster Presentation: Sunday, December
8, 2019 at 6:00 p.m.
EST
A new integrated analysis with up to six years of follow-up from
the Phase 3 RESONATE (PCYC-1112) and RESONATE-2 (PCYC-1115/1116)
studies evaluating IMBRUVICA monotherapy in previously untreated
patients (n=136; median age of 73 years) and R/R patients (n=135;
median age of 65 years for patients with 1-2 prior lines; median
age of 67 years for patients with 3 or more lines) with CLL will be
presented. Results reported IMBRUVICA monotherapy demonstrated
improved PFS, OS and ORR, with sustained efficacy for the
first-line patient group, including patients with high-risk
prognostic features, compared to the R/R group.
At up to six years of follow-up (first-line group: median of
59.8 months; 1-2 prior lines: 66.2 months; 3 or more prior lines:
65.1 months), the median PFS was not reached for the first-line or
the 1-2 prior lines groups, and median PFS was 40.1 months for the
3 or more prior lines group. A greater portion of patients treated
with IMBRUVICA in earlier lines remained progression-free or alive
at 60 months (first-line: 70 percent; 1-2 prior lines: 60 percent;
3 or more prior lines: 33 percent), and first-line treatment
resulted in a 34 percent reduction in risk of disease progression
or death compared to patients who had 1-2 prior lines of therapy
(HR: 0.66; 95 percent CI, 0.40 – 1.09). PFS was significantly
prolonged for patients receiving first-line treatment compared to
those who have received 3 or more prior therapy (HR: 0.32; 95
percent CI, 0.21 – 0.49). Furthermore, median OS for the first-line
or 1-2 prior lines group was not reached and was 67.4 months for
the 3 or more prior lines group. At 60 months, the ORR was 92
percent (first-line), 96 percent (1-2 prior lines) and 88 percent
(3 or more prior lines).
At the time of analysis, 58 percent of patients remain on
IMBRUVICA in the first-line group. Overall, 6 percent of patients
in the first-line group discontinued due to progressive disease,
while it was the most common reason for discontinuation for
patients who received 1-2 prior lines of therapy (22 percent) and
for those who received 3 or more prior lines (37 percent). Across
all three groups, 19 percent of patients discontinued due to AEs
(first-line: 21 percent; 1-2 prior: 19 percent; 3 or more prior: 15
percent).
About IMBRUVICA
IMBRUVICA (ibrutinib) is an oral, once-daily medicine that works
differently than chemotherapy as it blocks a protein called
Bruton's tyrosine kinase (BTK). The BTK protein sends important
signals that tell B cells to mature and produce antibodies. BTK
signaling is needed by specific cancer cells to multiply and
spread.1,2 By blocking BTK, IMBRUVICA may help move
abnormal B cells out of their nourishing environments in the lymph
nodes, bone marrow, and other organs.3
Since its launch in 2013, IMBRUVICA has received 10 FDA
approvals across six disease areas:
chronic lymphocytic leukemia (CLL) with or without 17p deletion
(del17p); small lymphocytic lymphoma (SLL) with or without del17p;
Waldenström's macroglobulinemia (WM); previously-treated patients
with mantle cell lymphoma (MCL)*; previously-treated patients with
marginal zone lymphoma (MZL) who require systemic therapy and have
received at least one prior anti-CD20-based therapy* – and
previously-treated patients with chronic graft-versus-host disease
(cGVHD) after failure of one or more lines of systemic
therapy.4
IMBRUVICA is now approved in 95 countries and has been used to
treat more than 170,000 patients worldwide across its approved
indications. IMBRUVICA is the only FDA-approved medicine in WM and
cGVHD. 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. IMBRUVICA was one of the
first medicines to receive FDA approval via the Breakthrough
Therapy Designation pathway.
The NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for CLL recommends ibrutinib
(IMBRUVICA®) as a preferred regimen for the initial
treatment of CLL/SLL and it is the only Category 1 single-agent
regimen for treatment-naïve patients without deletion 17p.
IMBRUVICA is being studied alone and in combination with other
treatments in several blood and solid tumor cancers and other
serious illnesses. IMBRUVICA is the most comprehensively studied
BTK inhibitor, with more than 150 ongoing clinical trials. 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. For more
information, visit www.IMBRUVICA.com.
*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.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Major hemorrhage
(≥ Grade 3, serious, or any central nervous system events;
e.g., intracranial hemorrhage [including subdural hematoma],
gastrointestinal bleeding, hematuria, and post procedural
hemorrhage) have occurred in 4% of patients, with fatalities
occurring in 0.4% of 2,838 patients exposed to
IMBRUVICA® in 27 clinical trials. Bleeding events
of any grade, including bruising and petechiae, occurred in 39% of
patients treated with IMBRUVICA®.
The mechanism for the bleeding events is not well
understood.
Use of either anticoagulant or antiplatelet agents concomitantly
with IMBRUVICA® increases the risk of major hemorrhage.
In IMBRUVICA® clinical trials, 3.1% of patients taking
IMBRUVICA® without antiplatelet or anticoagulant therapy
experienced major hemorrhage. The addition of antiplatelet
therapy with or without anticoagulant therapy increased this
percentage to 4.4%, and the addition of anticoagulant therapy with
or without antiplatelet therapy increased this percentage to
6.1%. Consider the risks and benefits of anticoagulant or
antiplatelet therapy when co-administered with
IMBRUVICA®. Monitor for signs and symptoms 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 1,124 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 1,124 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 of any grade occurred in
12% of 1,124 patients treated with IMBRUVICA® in
clinical trials. Grade 3 or greater hypertension occurred in 5% of
patients with a median time to onset of 5.9 months (range, 0.03 to
24 months).
Monitor blood pressure in patients treated with
IMBRUVICA® and initiate or adjust anti-hypertensive
medication throughout treatment with IMBRUVICA® as
appropriate.
Second Primary Malignancies: Other malignancies
(10%) including non-skin carcinomas (4%) have occurred in 1,124
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%)*, diarrhea (41%),
anemia (38%)*, neutropenia (35%)*, musculoskeletal pain (32%), rash
(32%), bruising (31%), nausea (26%), fatigue (26%), hemorrhage
(24%), 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 (18%)*, thrombocytopenia (16%)*, and pneumonia
(14%).
Approximately 7% (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%)*, muscle spasms (29%),
stomatitis (29%), nausea (26%),
hemorrhage (26%), anemia (24%)*, and pneumonia
(21%).
The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were
pneumonia (14%), fatigue (12%), diarrhea (10%),
neutropenia (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.
DRUG INTERACTIONS
CYP3A Inhibitors: Co-administration of
IMBRUVICA® with strong or moderate CYP3A inhibitors may
increase ibrutinib plasma concentrations. Dose modifications of
IMBRUVICA® may be recommended when used concomitantly
with posaconazole, voriconazole, and moderate CYP3A inhibitors.
Avoid concomitant use of other strong CYP3A inhibitors. Interrupt
IMBRUVICA® if strong inhibitors are used short-term
(e.g., for ≤ 7 days). See dose modification guidelines in USPI
sections 2.4 and 7.1.
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 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.
SOURCE AbbVie Inc.
|
1 Genetics Home Reference. Isolated
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2 Turetsky, et al. Single cell
imaging of Bruton's Tyrosine Kinase using an irreversible
inhibitor. Scientific Reports. volume 4, Article number: 4782
(2014).
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3 de
Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK
inhibitor PCI-32765 targets B-cell receptor- and
chemokine-controlled adhesion and migration in chronic lymphocytic
leukemia. Blood. 2012;119(11):2590-2594.
|
4 IMBRUVICA U.S.
Prescribing Information, September 2019.
|
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SOURCE AbbVie