NORTH CHICAGO, Ill.,
Dec. 23, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV) announced today that the U.S. Food and
Drug Administration (FDA) approved the update of the
IMBRUVICA® (ibrutinib) Prescribing Information to
include efficacy and safety data for the combination of IMBRUVICA
with rituximab for the treatment of Waldenström's macroglobulinemia
(WM), based on the final analysis of the Phase 3 iNNOVATE study.
First approved in 2013, IMBRUVICA is currently available to
patients with several types of blood cancer, as well as chronic
graft-versus-host disease. It was approved as a monotherapy for WM
in 2015 and as a combination therapy with rituximab in 2018 based
on the iNNOVATE primary analysis.
"We're encouraged by this latest recognition from the FDA as it
underscores our commitment to supporting those impacted by
Waldenström's macroglobulinemia, a rare and incurable form of
non-Hodgkin's lymphoma," said Danelle
James, M.D., M.A.S., IMBRUVICA Global Development Lead,
Pharmacyclics LLC, an AbbVie company. "IMBRUVICA is the only
FDA-approved treatment for these patients and now includes more
than five years of safety and efficacy data to help provide better
understanding of how to treat this rare blood cancer."
As of today, IMBRUVICA is the only Bruton's tyrosine kinase
(BTK) inhibitor approved to treat WM. WM typically affects older
adults and is primarily found in the bone marrow, although lymph
nodes and the spleen may also be affected. In the U.S., there are
approximately 2,800 new cases of WM each year.1 The
National Comprehensive Cancer Network®
(NCCN®), a not-for-profit alliance of 28 leading cancer
centers devoted to patient care, research, and education,
recommends IMBRUVICA, with or without rituximab, as the only
Category 1 Preferred regimen for patients with previously untreated
or previously treated WM.2
"The long-term results from the Phase 3 iNNOVATE study provide
clinicians even more evidence that patients with WM can benefit
from treatment with an ibrutinib-based regimen and maintain
prolonged progression-free survival," said Dr. Meletios A. Dimopoulos, Professor and Chairman
of the Department of Clinical Therapeutics, National and
Kapodistrian University of Athens School of Medicine, Athens, Greece, and principal
The IMBRUVICA Prescribing Information now includes final
analysis data, with an overall follow-up of 63 months, from the
Phase 3 iNNOVATE clinical trial. With additional
follow-up since the primary analysis, the combination of IMBRUVICA
plus rituximab continued to demonstrate prolonged progression-free
survival (PFS) in WM patients compared to
rituximab monotherapy. Patients treated in the IMBRUVICA arm
experienced a 75 percent reduction in risk of disease progression
or death compared to rituximab monotherapy (hazard ratio [HR]
0.25; 95% confidence interval [CI]:
0.15-0.42; p<0.0001). Results from the final analysis
of the study were recently featured as an oral presentation at the
2020 American Society of Hematology (ASH) Annual Meeting (Abstract
In the iNNOVATE study primary analysis, the most common side
effects (≥20%) in patients treated with IMBRUVICA plus rituximab
were bruising, muscle pain, bleeding problems, diarrhea, rash,
joint pain, nausea and high blood pressure.
iNNOVATE (PCYC-1127) is a Pharmacyclics-sponsored, randomized,
placebo-controlled, double-blind, Phase 3 study, which enrolled 150
patients with relapsed/refractory and treatment-naïve Waldenström's
macroglobulinemia. All patients received intravenous rituximab 375
mg/m2 once weekly for four consecutive weeks, followed
by a second four-weekly rituximab course following a three-month
interval. Patients were randomized to receive either ibrutinib 420
mg or placebo once daily continuously until criteria for treatment
discontinuation were met. The primary endpoint was progression-free
survival; secondary endpoints included overall response rate;
hematological improvement measured by hemoglobin; time-to-next
treatment; overall survival; and number of participants with
adverse events as a measure of safety and tolerability within each
IMBRUVICA is a once-daily,
first-in-class BTK inhibitor that is administered orally, and is
jointly developed and commercialized by Pharmacyclics, LLC, an
AbbVie Company, and Janssen Biotech, Inc. (Janssen). 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.3,4 By blocking BTK,
IMBRUVICA may help move abnormal B cells out of their nourishing
environments in the lymph nodes, bone marrow, and other
Since its launch in 2013, IMBRUVICA has received 11 FDA
approvals across six disease areas: chronic lymphocytic leukemia
(CLL) with or without 17p deletion (del17p); small lymphocytic
lymphoma (SLL) with or without del17p; 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.6
IMBRUVICA is now approved in 101 countries and has been used to
treat more than 200,000 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.
As of early 2019, the National Comprehensive Cancer
Network® (NCCN®), a not-for-profit alliance
of 28 leading cancer centers devoted to patient care, research, and
education, recommends ibrutinib (IMBRUVICA) as a preferred regimen
for the initial treatment of CLL/SLL and is a Category 1 treatment
for treatment-naïve patients without deletion 17p. In January 2020, the NCCN Guidelines®
were updated to recommend IMBRUVICA, with or without rituximab, as
a preferred regimen for the treatment of relapsed/refractory MCL,
regardless of response duration to prior chemoimmunotherapy. In
September 2020, the NCCN guidelines
for WM were updated and now recommends IMBRUVICA, with or without
rituximab, as the only Category 1 Preferred regimen for patients
with previously untreated or previously treated WM.
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 Side Effect Information
Before taking IMBRUVICA®, tell your
healthcare provider about all of your medical conditions, including
- have had recent surgery or plan to have surgery. Your
healthcare provider may stop IMBRUVICA® for any planned
medical, surgical, or dental procedure.
- have bleeding problems.
- have or had heart rhythm problems, smoke, or have a medical
condition that increases your risk of heart disease, such as high
blood pressure, high cholesterol, or diabetes.
- have an infection.
- have liver problems.
- are pregnant or plan to become pregnant. IMBRUVICA®
can harm your unborn baby. If you are able to become pregnant, your
healthcare provider will do a pregnancy test before starting
treatment with IMBRUVICA®. Tell your healthcare provider
if you are pregnant or think you may be pregnant during treatment
- Females who are able to become pregnant should use
effective birth control (contraception) during treatment with
IMBRUVICA® and for 1 month after the last dose.
- Males with female partners who are able to become
pregnant should use effective birth control, such as condoms,
during treatment with IMBRUVICA® and for 1 month after
the last dose.
- are breastfeeding or plan to breastfeed. Do not breastfeed
during treatment with IMBRUVICA® and for 1 week after
the last dose.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements. Taking
IMBRUVICA® with certain other medicines may affect
how IMBRUVICA® works and can cause side
How should I take IMBRUVICA®?
- Take IMBRUVICA® exactly as your healthcare provider
tells you to take it.
- Take IMBRUVICA® 1 time a day.
- Swallow IMBRUVICA® capsules or tablets whole with a
glass of water.
- Do not open, break or chew IMBRUVICA® capsules.
- Do not cut, crush or chew IMBRUVICA® tablets.
- Take IMBRUVICA® at about the same time each
- If you miss a dose of IMBRUVICA® take it as soon as
you remember on the same day. Take your next dose of
IMBRUVICA® at your regular time on the next day. Do not
take extra doses of IMBRUVICA® to make up for a missed
- If you take too much IMBRUVICA® call your healthcare
provider or go to the nearest hospital emergency room right
What should I avoid while taking
- You should not drink grapefruit juice, eat grapefruit, or eat
Seville oranges (often used in
marmalades) during treatment with IMBRUVICA®. These
products may increase the amount of IMBRUVICA® in your
What are the possible side effects of
IMBRUVICA® may cause serious side
- Bleeding problems (hemorrhage) are common during
treatment with IMBRUVICA®, and can also be serious and
may lead to death. Your risk of bleeding may increase if you are
also taking a blood thinner medicine. Tell your healthcare provider
if you have any signs of bleeding, including: blood in your stools
or black stools (looks like tar), pink or brown urine, unexpected
bleeding, or bleeding that is severe or that you cannot control,
vomit blood or vomit looks like coffee grounds, cough up blood or
blood clots, increased bruising, dizziness, weakness, confusion,
change in your speech, or a headache that lasts a long time or
- Infections can happen during treatment with
IMBRUVICA®. These infections can be serious and
may lead to death. Tell your healthcare provider right away if you
have fever, chills, weakness, confusion, or other signs or symptoms
of an infection during treatment with IMBRUVICA®.
- Decrease in blood cell counts. Decreased blood counts
(white blood cells, platelets, and red blood cells) are common with
IMBRUVICA®, but can also be severe. Your
healthcare provider should do monthly blood tests to check your
- Heart problems. Serious heart rhythm problems
(ventricular arrhythmias, atrial fibrillation, and atrial flutter),
heart failure, and death have happened in people treated with
IMBRUVICA®, especially in people who have an increased
risk for heart disease, have an infection, or who have had heart
rhythm problems in the past. Tell your healthcare provider if you
get any symptoms of heart problems, such as feeling as if your
heart is beating fast and irregular, lightheadedness, dizziness,
shortness of breath, swelling of the feet, ankles, or legs,
chest discomfort, or you faint. If you develop any of these
symptoms, your healthcare provider may do a test to check your
heart (ECG) and may change your IMBRUVICA® dose.
- High blood pressure (hypertension). New or
worsening high blood pressure has happened in people treated with
IMBRUVICA®. Your healthcare provider may start you on
blood pressure medicine or change current medicines to treat your
- Second primary cancers. New cancers have happened
during treatment with IMBRUVICA®, including cancers of
the skin or other organs.
- Tumor lysis syndrome (TLS). TLS is caused by the fast
breakdown of cancer cells. TLS can cause kidney failure and the
need for dialysis treatment, abnormal heart rhythm, seizure, and
sometimes death. Your healthcare provider may do blood tests to
check you for TLS.
The most common side effects of
IMBRUVICA® in adults with B-cell
malignancies (MCL, CLL/SLL, WM and MZL) include:
- muscle and bone pain
The most common side effects of IMBRUVICA® in
adults with cGVHD include:
- mouth sores (stomatitis)
- muscle spasms
Diarrhea is a common side effect in people who take
IMBRUVICA®. Drink plenty of fluids during
treatment with IMBRUVICA® to help reduce
your risk of losing too much fluid (dehydration) due to diarrhea.
Tell your healthcare provider if you have diarrhea that does not go
These are not all the possible side effects of
IMBRUVICA®. Call your doctor for medical advice about
side effects. You may report side effects to FDA at
General information about the safe and effective use of
Medicines are sometimes prescribed for purposes other than those
listed in a Patient Information leaflet. Do not use
IMBRUVICA® for a condition for which it was not
prescribed. Do not give IMBRUVICA® to other people,
even if they have the same symptoms that you have. It may harm
them. You can ask your pharmacist or healthcare provider for
information about IMBRUVICA® that is written for
Please click here
for full Prescribing Information.
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deliver innovative medicines that solve serious health issues today
and address the medical challenges of tomorrow. We strive to have a
remarkable impact on people's lives across several key therapeutic
areas: immunology, oncology, neuroscience, eye care, virology,
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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, competition from
other products, challenges to intellectual property, 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 2019 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 Lymphoma Research Foundation. Waldenström's
Macroglobulinemia. https://lymphoma.org/aboutlymphoma/nhl/wm/. Accessed
2 National Comprehensive Cancer Network. NCCN
Clinical Practice Guidelines in Oncology Version 1.2021
Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma.
3 Genetics Home Reference. Isolated growth hormone
Accessed June 2020.
4 Turetsky, et al. Single cell imaging of Bruton's
Tyrosine Kinase using an irreversible inhibitor. Scientific
Reports. volume 4, Article number: 4782 (2014).
5 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.
6 IMBRUVICA U.S. Prescribing
Information, December 2020.