SUNNYVALE, Calif., May 22, 2015 /PRNewswire/ -- Pharmacyclics,
Inc. (NASDAQ: PCYC) announced today that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMA) issued a positive opinion recommending a change to the
terms of the marketing authorization for IMBRUVICA®
(ibrutinib) in the European Union to indicate the treatment of
adult patients with Waldenström's macroglobulinemia (WM) who have
received at least one prior therapy, or in first line treatment for
patients unsuitable for chemo-immunotherapy.1 WM is a
rare, slow growing form of blood cancer.2 IMBRUVICA is
also the first and only FDA-approved treatment for WM in
the United States.3 The
CHMP recommendation follows the January
2015 U.S. Food and Drug Administration (FDA) full approval
of IMBRUVICA to treat all lines of patients with WM.
IMBRUVICA is jointly developed and commercialized in
the United States by Pharmacyclics
and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV
(Janssen) holds the marketing authorization and its affiliates
market IMBRUVICA in EMEA (Europe,
Middle East, Africa), as well as the rest of the world.
IMBRUVICA is already approved in Europe to treat adult patients with relapsed
or refractory mantle cell lymphoma (MCL) and adult patients with
chronic lymphocytic leukemia (CLL) who have received at least one
prior therapy or in first line in the presence of 17p deletion or
TP53 mutation in patients unsuitable for chemo-immunotherapy.
The European Medicines Agency is an agency of
the European Union responsible for the scientific
evaluation of medicines submitted for approval by pharmaceutical
companies for use in the 28 countries of the European Union.
The positive CHMP opinion will be reviewed by the European
Commission, and a final decision on IMBRUVICA to treat WM is
anticipated in the second half of 2015. In addition to European
markets, a worldwide regulatory filing program for IMBRUVICA
currently is underway.
"We are very pleased that patients with WM in the European Union
will have a first-in-class, oral, single-agent, non-chemotherapy
treatment option in IMBRUVICA," said Thorsten Graef, M.D., Ph.D., Head of Hematology
at Pharmacyclics. "This approval underscores the compelling safety
and efficacy profile of IMBRUVICA in hematologic malignancies and
we look forward to addressing the unmet medical needs of WM
patients across Europe."
WM currently affects approximately 23,000 patients in the G7
countries (United States,
France, Germany, Italy, Japan
and the United
Kingdom).3 The CHMP recommendation was based on a
multi-center, Phase II study that evaluated the efficacy and
tolerability of IMBRUVICA in 63 patients with previously treated
WM. Initial data from the study submitted for review in the EU
showed an overall response rate (ORR) of 87.3% after a
median duration of treatment of 11.7 months.
Updated results from the study were published on in the
April 9, 2015 edition of The New
England Journal of Medicine, indicating an ORR of 90.5% after a
median duration of treatment of 19.1 months using criteria adopted
from the International Workshop on WM. At 24 months, the estimated
rate of progression-free survival was 69.1% (95% CI, 53.2 to 80.5),
and the estimated rate of overall survival was 95.2% (95% CI, 86.0
to 98.4).
No new safety issues were observed in the clinical trial. The
most commonly occurring adverse reactions in WM patients treated
with IMBRUVICA (>20%) were neutropenia and thrombocytopenia.
Other adverse reactions occurred in <10% of patients (n=5). Six
percent of patients receiving IMBRUVICA in the WM trial
discontinued treatment due to neutropenia or thrombocytopenia. Of
note, IMBRUVICA-related neutropenia and thrombocytopenia were
reversible, but required a reduction in dose and/or discontinuation
of treatment with IMBRUVICA in three of the four patients who
developed these conditions. Overall, IMBRUVICA was well tolerated
and there were no unexpected toxicities.
About Waldenström's macroglobulinemia
WM (a clinically recognized subset of lymphoplasmacytic
lymphoma, or LPL) is a slow-growing and rare blood cancer that most
commonly originates from B cells, a type of white blood cell
(lymphocyte) that develops in the bone marrow.2 WM
occurs as the result of a malfunction in the healthy lifecycle of a
B cell, causing the cell to become malignant and reproduce at an
abnormal rate. The malignant B cells produce large amounts of an
abnormal type of antibody protein called immunoglobulin M
(IgM). Excess IgM causes the blood to thicken and causes many
of the symptoms of WM.2
About IMBRUVICA
IMBRUVICA is currently approved
in the United States for the
treatment of patients with chronic lymphocytic leukemia (CLL) who
have received at least one prior therapy, all CLL patients
(including treatment naïve) who have del 17p, a genetic mutation
that occurs when part of chromosome 17 has been lost, and all
patients (including treatment naïve) with Waldenström's
macroglobulinemia. IMBRUVICA is also
approved under accelerated approval for the treatment of patients
with mantle cell lymphoma (MCL) who have received at least one
prior therapy.3
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily
therapy that inhibits a protein called Bruton's tyrosine kinase
(BTK).3 IMBRUVICA was one of the first medicines to
receive U.S. FDA approval via the new Breakthrough Therapy
Designation pathway, and is the only product to have received three
Breakthrough Therapy Designations.
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.3,5 IMBRUVICA blocks signals that tell
malignant B cells to multiply and spread
uncontrollably.3
IMBRUVICA is being studied alone and in combination with other
treatments in several blood cancers. More than 6,100 patients have
been treated in clinical trials of IMBRUVICA conducted in 35
countries by more than 800 investigators. Currently, 13 Phase III
trials have been initiated with IMBRUVICA and 67 trials are
registered on www.clinicaltrials.gov.
To learn more about the medical terminology used in this news
release, please visit
http://stedmansonline.com/.
INDICATIONS
IMBRUVICA is indicated in the U.S. to treat people with:
- Chronic lymphocytic leukemia (CLL) who have received at least
one prior therapy
- Chronic lymphocytic leukemia (CLL) with 17p deletion
- Waldenström's macroglobulinemia
- Mantle cell lymphoma (MCL) who have received at least one prior
therapy – accelerated approval was granted for this indication
based on overall response rate. Continued approval for this
indication may be contingent upon verification of clinical benefit
in confirmatory trials.
Patients taking IMBRUVICA for CLL or WM should take 420 mg taken
orally once daily (or three 140 mg capsules once daily).
Patients taking IMBRUVICA for MCL should take 560 mg taken
orally once daily (or four 140 mg capsules once daily).
Capsules should be taken orally with a glass of water. Capsules
should be taken whole. Do not open, break, split or chew the
capsules.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage - Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Grade 3 or higher
bleeding events (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.
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 have occurred
with IMBRUVICA® therapy. Grade 3 or greater infections
occurred in 14% to 26% of patients. Cases of progressive multifocal
leukoencephalopathy (PML) have occurred in patients treated with
IMBRUVICA®. Monitor patients for fever and infections
and evaluate promptly.
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%) occurred in patients treated
with 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, acute infections, and a previous history of atrial
fibrillation. Periodically monitor patients clinically for atrial
fibrillation. Patients who develop arrhythmic symptoms (e.g.,
palpitations, lightheadedness) or new-onset dyspnea should have an
ECG performed. If atrial fibrillation persists, consider the risks
and benefits of IMBRUVICA® treatment and dose
modification.
Second Primary Malignancies - Other malignancies (range,
5 to 14%) including non-skin carcinomas (range, 1 to 3%) have
occurred in patients treated with IMBRUVICA®. The most
frequent second primary malignancy was non-melanoma skin cancer
(range, 4 to 11%).
Tumor Lysis Syndrome - Tumor lysis syndrome has been
reported with IMBRUVICA® therapy. Monitor patients
closely and take appropriate precautions in patients at risk for
tumor lysis syndrome (e.g., high tumor burden).
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®. 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 (>25%) in patients with
B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%,
52%, 43%), neutropenia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%),
anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), musculoskeletal
pain (37%, 28%**, NA***), bruising (30%, 12%**, 16%**), nausea
(31%, 26%, 21%), upper respiratory tract infection (34%, 16%, 19%),
and rash (25%, 24%**, 22%**).
*Based on adverse reactions and/or laboratory measurements
(noted as platelets, neutrophils, or hemoglobin decreased).
**Includes multiple ADR terms.
***Not applicable; no associated ADRs.
The most common Grade 3 or 4 non-hematological 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 events.
Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients
discontinued due to adverse events. Most frequent adverse events
leading to discontinuation were infections, subdural hematomas, and
diarrhea in CLL patients and subdural hematoma (1.8%) in MCL
patients
DRUG INTERACTIONS
CYP3A Inhibitors - Avoid co-administration with strong
and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must
be used, reduce the IMBRUVICA® dose.
CYP3A Inducers - Avoid co-administration 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:
http://www.imbruvica.com/downloads/Prescribing_Information.pdf.
About Pharmacyclics
Pharmacyclics, Inc. (NASDAQ: PCYC) is a biopharmaceutical
company focused on developing and commercializing innovative
small-molecule drugs for the treatment of cancer and immune
mediated diseases. The company's mission is to build a viable
biopharmaceutical company that designs, develops and commercializes
novel therapies intended to improve quality of life, increase
duration of life and resolve serious unmet medical needs. It will
do so by identifying and controlling promising product candidates
based on scientific development and administrative expertise,
developing its products in a rapid, cost-efficient manner and,
pursuing commercialization and/or development partners when and
where appropriate.
Pharmacyclics markets IMBRUVICA and has three product candidates
in clinical development and several preclinical molecules in lead
optimization. The company is committed to high standards of ethics,
scientific rigor and operational efficiency as it moves each of
these programs to commercialization. Pharmacyclics is headquartered
in Sunnyvale, CA. To learn more,
please visit www.pharmacyclics.com.
NOTE: This announcement may contain forward-looking
statements made in reliance upon the safe harbor provisions of
Section 27A of the Securities Act of 1933, as amended, and Section
21E of the Securities Exchange Act of 1934, as amended, including
statements, among others, relating to our future capital
requirements, including our expected liquidity position and timing
of the receipt of certain milestone payments, and the sufficiency
of our current assets to meet these requirements, our future
results of operations, our expectations for and timing of ongoing
or future clinical trials and regulatory approvals for any of our
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are subject to risks and uncertainties. When used in this
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"plan", "predict", "intend", "target" and similar expressions are
intended to identify such forward-looking statements. These
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and other factors that could cause our actual results, performance,
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Factors that may cause such a difference include, without
limitation, our need for substantial additional financing and the
availability and terms of any such financing, the safety and/or
efficacy results of clinical trials of our product candidates, our
failure to obtain regulatory approvals or comply with ongoing
governmental regulation, our ability to commercialize, manufacture
and achieve market acceptance of any of our product candidates, for
which we rely heavily on collaboration with third parties, and our
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given that the actual results will be consistent with these
forward-looking statements. For more information about the risks
and uncertainties that may affect our results, please see the Risk
Factors section of our filings with the Securities and Exchange
Commission, including our Form 10-K for the year ended December 31, 2013 and quarterly reports on Form
10-Q. We do not intend to update any of the forward-looking
statements after the date of this announcement to conform these
statements to actual results, to changes in management's
expectations or otherwise, except as may be required by law.
IMBRUVICA is a registered trademark of Pharmacyclics, Inc.
1 European Medicines Agency. Committee for Medicinal
Products for Human Use: Summary of opinion. Available at
http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/003791/WC500187054.pdf.
Last accessed May 2015.
2 American Cancer Society. "What is Waldenstrom
macroglobulinemia?" Available at:
http://www.cancer.org/cancer/waldenstrommacroglobulinemia/detailedguide/waldenstrom-macroglobulinemia-w-m.
Accessed May 2015.
3 IMBRUVICA Prescribing Information, January
2015
4 Decision Resources. 2012.
5 Genetics Home Reference. Isolated growth hormone
deficiency. Available at:
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed May 2015.
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SOURCE Pharmacyclics, Inc.