NORTH CHICAGO, Ill.,
Dec. 6, 2016 /PRNewswire/
-- AbbVie (NYSE: ABBV), a global biopharmaceutical company,
today announced positive results from a Phase 2 study (PCYC-1129)
evaluating ibrutinib (IMBRUVICA®) in patients with
chronic graft-versus-host-disease (cGVHD), a serious and
debilitating potential consequence of stem cell or bone marrow
transplant,1 who failed prior systemic therapy. The
study found ibrutinib demonstrated efficacy, sustained responses
and reduced symptom severity, with an overall response rate (ORR)
of 67%.2 Final results from this study presented today
as a late-breaking oral presentation at the 58th
American Society of Hematology (ASH) Annual Meeting and Exposition
in San Diego, CA (abstract
#LBA-3). 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.
At a median follow-up of 14 months in 42 patients, the study
found an ORR of 67%. One-third of all responders achieved a
complete response (CR). In addition, 71% of patients showed a
sustained response of at least 5 months. Similar response rates
were seen across all involved organs, and patients with multiple
organ involvement generally responded in multiple organs. Over the
course of the study, 61% of responders experienced a clinically
meaningful improvement in symptoms, as measured by at least a
7-point decrease in Lee Symptom Scale score. In addition, 62% of
all patients were able to reduce steroid dose to an acceptable
minimal level and five completely discontinued steroids with
response. Twelve patients (29%) remain on treatment with
ibrutinib.2
"These results are encouraging as they suggest ibrutinib has
clinically meaningful potential in patients with steroid-refractory
chronic graft-versus-host-disease," said David Miklos, M.D., Ph.D., Associate Professor
of Medicine (Blood and Marrow Transplantation), Stanford University and lead investigator of the
study.* "cGVHD patients face a challenging treatment journey with
the majority of patients being prescribed steroids, with which
long-term use can lead to serious health complications. With no
FDA-approved therapies available specifically for cGVHD, new
treatment options are critically needed."
GVHD is a life-threatening condition in which the body is
attacked by donor immune cells after a patient undergoes an
allogeneic stem cell or bone marrow transplant.1,3 GVHD
can be acute or chronic; chronic GVHD (cGVHD) usually starts more
than 3 months after a transplant and can last many
years.3 Symptoms can include skin problems, hair loss,
mouth sores, eye irritation, severe lung injury, or liver
dysfunction.3 There are currently no therapies
specifically approved for patients with cGVHD who have failed
first-line corticosteroid therapy and require additional therapy.
Most patients with cGVHD are prescribed high dose glucocorticoids,
a systemic steroid that suppresses the immune system and is
associated with substantial morbidity and relapse of the underlying
disease.3
"Ibrutinib works as a BTK inhibitor, which is showing to have a
potential impact beyond blood cancers, including chronic
graft-versus-host-disease," said Lori Styles, M.D., Senior
Medical Director and GVHD program clinical lead at Pharmacyclics
LLC, an AbbVie company. "We recognize the critical need for new
treatments for patients with cGVHD and are encouraged by the
results of this well-designed study, giving us confidence to
proceed with a Phase 3 trial evaluating the impact of ibrutinib as
part of initial therapy for this severe and potentially
life-threatening condition. We are committed to exploring the full
potential of ibrutinib in a range of health conditions with unmet
needs."
The U.S. Food and Drug Administration (FDA) granted Breakthrough
Therapy Designation and Orphan Drug Designation in June 2016 for
ibrutinib as a potential treatment for cGVHD after failure of one
or more lines of systemic therapy.
About the Study
PCYC-1129 evaluated the safety and
efficacy of ibrutinib in 42 patients (median age 56 years) with
cGVHD who failed at least one prior therapy, including
corticosteroids. Patients were treated with ibrutinib once daily
until cGVHD progression or unacceptable toxicity. The primary
endpoint was cGVHD response based on the National Institutes of
Health (NIH) consensus response criteria. Secondary endpoints
included rate of sustained response, change in Lee cGVHD Symptom
Scale, changes in corticosteroid requirement over time, and safety
endpoints. Overall, reported adverse events (AEs) were consistent
with those treated with ibrutinib for B-cell malignancies and in
patients with cGVHD on corticosteroids.2
The most common AEs were fatigue (57%), diarrhea (36%), muscle
spasms (29%), nausea (26%), and bruising (24%). Serious AEs (SAEs)
occurred in 22 patients (52%), including pneumonia (n=6), septic
shock (n=2), and pyrexia (n=2).2
Preliminary results from this trial were previously presented at
the 42nd Annual Meeting of the European Society for
Blood and Marrow Transplantation (ESBM) in April 2016 and the 51st American
Society of Clinical Oncology (ASCO) Annual Meeting in May 2015.
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 MCL who have received at
least one prior therapy and patients with WM. 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 in 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. Miklos served as an investigator of
this Pharmacyclics-sponsored clinical study. Dr. Miklos does not
have a financial interest in the company.
1 MedlinePlus, U.S. National Library of Medicine.
Graft-versus-host-disease. Available from:
http://www.nlm.nih.gov/medlineplus/ency/article/001309.htm.
Accessed March 2016.
2 Miklos, D, et al. Multicenter Open-Label Phase 2 Study
of Ibrutinib in Chronic Graft Versus Host Disease (cGVHD) After
Failure of Corticosteroids. ASH 2016 Abstract #LBA-3.
3 The Leukemia and Lymphoma Society. Graft Versus Host
Disease. Available from:
http://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/graft-versus-host-disease.
4 IMBRUVICA US Prescribing Information, May
2016.
5 Genetics Home Reference. Isolated growth hormone
deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed May 2016.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/late-breaking-ibrutinib-imbruvica-data-show-complete-or-partial-response-in-two-thirds-of-patients-with-chronic-graft-versus-host-disease-a-frequent-and-potentially-life-threatening-complication-of-stem-cell-transplant-300373632.html
SOURCE AbbVie