NORTH CHICAGO, Ill.,
Feb. 28, 2022 /PRNewswire/ -- AbbVie
(NYSE: ABBV), today announced the submission of a supplemental New
Drug Application (sNDA) to the U.S. Food and Drug Administration
(FDA) for IMBRUVICA® (ibrutinib) for the treatment of
pediatric and adolescent patients one year and older with chronic
graft versus host disease (cGVHD) after failure of one or more
lines of systemic therapy. A New Drug Application (NDA) was also
submitted for an oral suspension formulation of IMBRUVICA to
provide an alternative administration option for pediatric
patients. If approved, this represents AbbVie's first pediatric
indication for IMBRUVICA.
cGVHD is a life-threatening complication for about 14,000
patients each year after receiving a donor stem cell or bone marrow
transplantation.1,2 Nearly half of these transplant
patients develop cGVHD, and there are currently no FDA-approved
treatment options for children under 12.3 The
applications seek to update the IMBRUVICA U.S. Prescribing
Information primarily based on the analysis of three years of
data from the Phase 1/2 iMAGINE clinical trial, including use
of a new oral suspension formulation of the treatment.
"We are committed to this work with IMBRUVICA in the hopes of
providing the first FDA-approved BTKi treatment option for younger
patients with cGVHD, including a new oral suspension formulation,"
said James Dean, M.D., Ph.D.,
IMBRUVICA Global Development Lead and Executive Medical Director at
AbbVie. "For young children, the availability of a liquid oral
suspension versus an oral capsule or tablet can be significant to
enable them to take the recommended dose and address challenges
swallowing capsules or tablets."
The iMAGINE clinical trial enrolled 59 patients 1-19 years of
age with relapsed/refractory (R/R) or new-onset moderate/severe
cGVHD. The primary endpoints of the study were pharmacokinetics
(PK) and safety; secondary endpoints included overall response
rate. Results showed an overall response rate of 78 percent with
IMBRUVICA and that PK data was consistent with adult dosing of
IMBRUVICA. After 20 weeks, sustained response rates were observed
in 70 percent and 58 percent of treatment-naive and R/R responders,
respectively. Safety was consistent with the established profile
for IMBRUVICA, with observed adverse events (AEs) consistent with
those observed in adult patients with moderate to severe cGVHD. The
most common Grade ≥3 AEs (≥ 5% of subjects) overall were pyrexia
(8.5%), neutropenia (6.8%), stomatitis (6.8%), hypoxia (6.8%),
osteonecrosis (6.8%), alanine aminotransferase increased (5.1%),
hypokalemia (5.1%), and pneumothorax (5.1%).
"It is important to empower patients and their families with
evidence-based knowledge and I am encouraged by the results from
the iMAGINE clinical trial of IMBRUVICA," said Dr. Paul A. Carpenter, attending physician at
Seattle Children's Hospital and study principal investigator.
"Results show that PK and safety were consistent with the known
profile of IMBRUVICA and that of cGVHD. Efficacy results, including
sustained response rates, were also encouraging."
In 2017, IMBRUVICA was first approved as a single-agent therapy
for adult patients with cGVHD who have experienced failure of prior
systemic therapy, becoming the first FDA-approved treatment for
adults with cGVHD. IMBRUVICA could be the first FDA-approved BTKi
treatment option for pediatric and adolescent patients with
cGVHD.
About cGVHD
cGVHD occurs when donated peripheral blood or bone marrow stem
cells view the recipient's body as foreign and the donated
cells launch an immune attack on the body.4 cGVHD
impacts major organs, with the skin, eyes, mouth and liver being
most common.5 About 35 percent of the estimated
8,000 patients who undergo life-saving allogeneic Hematopoietic
Stem Cell Transplant (HSCT) per year develop cGVHD that requires
systemic treatment.4 Additionally, cGVHD is the most
common cause of morbidity after allogeneic transplant.6
Steroids are the current standard treatment for pediatric
cGVHD.7
About the iMAGINE Study
iMAGINE (PCYC-1146-IM) is an interventional single group
treatment Phase 1/2 study, which enrolled 59 pediatric patients
with chronic graft versus host disease (cGVHD). In the two-part
study, Part A patients ages one to <12 years with moderate or
severe cGVHD after failure of one or more lines of systemic therapy
received IMBRUVICA oral suspension or capsule starting at
120mg/m2 once daily. To determine the Recommended
Pediatric Equivalent Dose (RPED), dosage was escalated to
240mg/m2 after 14 days if no Grade 3 or higher related
toxicity was observed. In Part B, patients 12 to <22 years of
age with moderate or severe cGVHD who were newly diagnosed or had
failed one or more lines of systemic therapy were given 420mg
IMBRUVICA orally once daily. Once the RPED was determined in Part
A, patients 1 to <12 years of age with new-onset or
relapsed/refractory cGVHD could be enrolled in Part B.
Primary endpoints included pharmacokinetics (PK) and safety,
and secondary endpoints included overall response rate (ORR; CR/PR)
per 2014 NIH criteria, overall survival, duration of response
(DOR), and patient reported outcomes.
About IMBRUVICA
IMBRUVICA® (ibrutinib) is a once-daily oral
medication that is jointly developed and commercialized by
Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc.
IMBRUVICA® blocks the Bruton's tyrosine kinase (BTK)
protein, which is needed by normal and abnormal B cells, to
multiply and spread. By blocking BTK, IMBRUVICA may help move
abnormal B cells out of their nourishing environments in the lymph
nodes, bone marrow, and other organs.8,9,10
IMBRUVICA® is approved in more than 100 countries and
has been used to treat more than 250,000 patients worldwide. There
are more than 50 company-sponsored clinical trials, including 18
ongoing or completed Phase 3 studies, over 11 years evaluating the
efficacy and safety of IMBRUVICA®.
IMBRUVICA® was first approved by the U.S. Food and
Drug Administration (FDA) in November
2013, and today is indicated for adult patients in six
disease areas, including five hematologic cancers. These include
adults with CLL/small lymphocytic lymphoma (SLL) with or without
17p deletion (del17p) and adults with Waldenström's
macroglobulinemia (WM), as well as adult patients with previously
treated mantle cell lymphoma (MCL)*, adult patients with previously
treated marginal zone lymphoma (MZL) who require systemic therapy
and have received at least one prior anti-CD20-based therapy*, as
well as adult patients with previously treated chronic
graft-versus-host disease (cGVHD) after failure of one or more
lines of systemic therapy.11
*Accelerated approval was granted for MCL and MZL based on
overall response rate. Continued approval for MCL and MZL may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
Since 2019, the National Comprehensive Cancer
Network® (NCCN®), recommends ibrutinib
(IMBRUVICA®) as a preferred regimen for first-line
treatment of CLL/SLL, with Category 1 status for previously
untreated patients without del17p. Additionally,
IMBRUVICA® is a preferred treatment regimen for
previously untreated patients with del17p. Since January 2020, the NCCN Guidelines recommend
IMBRUVICA® as a category 2A preferred regimen for the
treatment of relapsed/refractory MCL. Since September 2020, the NCCN Guidelines recommend
IMBRUVICA® with or without rituximab as a Category 1
preferred regimen for both untreated and previously treated WM
patients.12
For more information, visit www.IMBRUVICA.com.
Important Side Effect Information
Before taking IMBRUVICA®, tell your
healthcare provider about all of your medical conditions,
including if you:
- 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
with IMBRUVICA®.
-
- 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
effects.
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
day.
- 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
dose.
- If you take too much IMBRUVICA® call your healthcare
provider or go to the nearest hospital emergency room right
away.
What should I avoid while taking
IMBRUVICA®?
- 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
blood.
What are the possible side effects of
IMBRUVICA®?
IMBRUVICA® may cause serious side
effects, including:
- 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
severe headache.
- 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
blood counts.
- 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
blood pressure.
- 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:
- diarrhea
- tiredness
- muscle and bone pain
- rash
- bruising
The most common side effects of
IMBRUVICA® in adults with cGVHD
include:
- tiredness
- bruising
- diarrhea
- mouth sores (stomatitis)
- muscle spasms
- nausea
- pneumonia
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
away.
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
1-800-FDA-1088.
General information about the safe and effective use of
IMBRUVICA®
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
health professionals.
Uses
What is
IMBRUVICA® (ibrutinib)?
IMBRUVICA® (ibrutinib) is a prescription
medicine used to treat adults with:
- Mantle cell lymphoma (MCL) who have received at least one prior
treatment
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma
(SLL)
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma
(SLL) with 17p deletion
- Waldenström's macroglobulinemia (WM)
- Marginal zone lymphoma (MZL) who require a medicine by
mouth or injection (systemic therapy) and have received a certain
type of prior treatment
- Chronic graft versus host disease (cGVHD) after failure of 1 or
more lines of systemic therapy
It is not known if IMBRUVICA® is safe and
effective in children.
Please see the full Important Product Information.
About AbbVie in Oncology
At AbbVie, we are committed
to transforming standards of care for multiple blood cancers while
advancing a dynamic pipeline of investigational therapies across a
range of cancer types. Our dedicated and experienced team joins
forces with innovative partners to accelerate the delivery of
potentially breakthrough medicines. We are evaluating more than 20
investigational medicines in over 300 clinical trials across some
of the world's most widespread and debilitating cancers. As we work
to have a remarkable impact on people's lives, we are committed to
exploring solutions to help patients obtain access to our cancer
medicines. For more information, please visit
http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and
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,
women's health and gastroenterology, in addition to products and
services across its Allergan Aesthetics portfolio. For more
information about AbbVie, please visit us at www.abbvie.com. Follow
@abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statements
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, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. 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 2021 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. 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 Leukemia and Lymphoma Society. Graft Versus Host
Disease. Available from:
https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/graft-versus-host-disease.
Accessed February 2021.
2 Bachier CR, Aggarwal SK, et al. Epidemiology and
Real-World Treatment of Chronic Graft-Versus-Host Disease Post
Allogeneic Hematopoietic Cell Transplantation: A US Claims
Analysis. Blood 2019; doi:
https://doi.org/10.1182/blood-2019-13056
3 Robert Zeiser,
Stephanie J Lee; Three FDA-approved therapies for chronic GVHD.
Blood 2022; blood.2021014448. doi:
https://doi.org/10.1182/blood.2021014448
4 Martin PJ, Lee SJ, Przepiorka D, et al. National
Institutes of Health Consensus Development Project on Criteria for
Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014
Clinical Trial Design Working Group Report. Biol Blood Marrow
Transplant. 2015;21(8):1343-1359.
doi:10.1016/j.bbmt.2015.05.004
5 Lee SJ. Classification systems for chronic
graft-versus-host disease. Blood. 2017;129(1):30-37.
doi:10.1182/blood-2016-07-686642
6 Cooke KR, Luznik L, Sarantopoulos S, et al. The
Biology of Chronic Graft-versus-Host Disease: A Task Force Report
from the National Institutes of Health Consensus Development
Project on Criteria for Clinical Trials in Chronic
Graft-versus-Host Disease. Biol Blood Marrow Transplant.
2017;23(2):211-234. doi:10.1016/j.bbmt.2016.09.023
7 Baird K, Cooke K, Schultz KR. Chronic
graft-versus-host disease (GVHD) in children. Pediatr Clin North
Am. 2010;57(1):297-322. doi:10.1016/j.pcl.2009.11.003
8 Genetics Home Reference. Isolated growth hormone
deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed November 2021.
9 Turetsky A, et al. Single cell imaging of Bruton's
tyrosine kinase using an irreversible inhibitor. Scientific
Reports. 2014;6:4782.
10 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.
11 IMBRUVICA U.S. Prescribing Information, December 2020.
12 NCCN® Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic
Lymphoma V4.2021. National Comprehensive Cancer Network. Accessed
November 2021.
View original
content:https://www.prnewswire.com/news-releases/abbvie-seeks-new-indication-for-imbruvica-ibrutinib-in-pediatric-patients-with-chronic-graft-versus-host-disease-cgvhd-301491494.html
SOURCE AbbVie