PHILADELPHIA, April 20, 2015 /PRNewswire/ -- Pharmacyclics,
Inc. (NASDAQ: PCYC) today announced that IMBRUVICA®
(ibrutinib) follow-up data in treatment-naive (TN) and
relapsed/refractory (R/R) patients with chronic lymphocytic
leukemia or small lymphocytic lymphoma (CLL or SLL, respectively)
demonstrated that, with up to 45 months of follow-up, the 94
patients (27 TN and 67 R/R) who received IMBRUVICA 420 mg
experienced a 91% overall response rate (ORR) and 14% of all
patients achieved a complete response (CR) (26% TN, 9% R/R). These
data are an analysis of outcomes from the Phase I/IIb study
(PCYC-1102) and the ongoing extension study (PCYC-1103) and were
presented in an oral presentation yesterday at the American
Association of Cancer Research (AACR) Annual Meeting in
Philadelphia, PA by Steven Coutre, M.D., Professor of Medicine,
Stanford University School of Medicine,
Stanford, CA. IMBRUVICA is jointly
developed and commercialized by Pharmacyclics and Janssen Biotech,
Inc.
The median treatment duration was 25 months (range, 0-45 months)
for all patients (30 months TN; 22 months R/R). The median duration
of response (DOR) and progression-free survival (PFS) have not yet
been reached. The 30-month PFS rate was 96% in TN and 76% in R/R
CLL patients. The median number of prior therapies for R/R patients
was four (range, 1-12 therapies). One patient with previously
untreated CLL experienced disease progression during the
follow-up.
"These data focused on the recommended 420 mg dose for CLL
patients and demonstrate the continued efficacy and tolerability of
IMBRUVICA, supporting its use as a longer-term, single-agent, oral
treatment option for patients with CLL," said Danelle James, M.D., M.S., Head of Oncology at
Pharmacyclics.
The majority of patients entered the study with baseline
cytopenias. Early and sustained improvement in hemoglobin and
platelet counts were observed. The most frequently reported Grade 3
or greater adverse events (AEs) in the trial were hypertension
(23%), pneumonia (15%), neutropenia (13%), atrial fibrillation (7%)
and diarrhea (7%). During follow-up, 12 patients discontinued
treatment due to disease progression. Discontinuation due to AEs
declined over time; in total, 12 patients discontinued due to an AE
(seven patients in year 1, three patients in year 2, and two
patients beyond year 3).
About Chronic Lymphocytic Leukemia (CLL)
The prevalence of CLL/SLL is approximately 115,000 patients in
the United States,1
with approximately 16,000 newly diagnosed patients every
year.2 As this orphan disease frequently progresses
following first-line therapy, patients are faced with fewer
treatment options and often are prescribed multiple lines of
therapy as they relapse or become resistant to
treatments.3
In CLL/SLL, the genetic mutation del 17p occurs when part of
chromosome 17 has been lost or deleted. CLL/SLL patients with del
17p have poor treatment outcomes.4 Del 17p is reported
in approximately 7% of treatment-naive CLL/SLL cases,5
and approximately 20% to 40% of relapsed/refractory patients harbor
the mutation.6
About IMBRUVICA
IMBRUVICA is currently approved
for the treatment of patients with chronic lymphocytic leukemia
(CLL) who have received at least one prior therapy, all CLL
patients (including treatment-naive) who have del 17p, a genetic
mutation that occurs when part of chromosome 17 has been lost, and
all patients (including treatment-naive) with Waldenstrom's
macroglobulinemia.7 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.7
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily
therapy that inhibits a protein called Bruton's tyrosine kinase
(BTK).7 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.7,8 IMBRUVICA blocks signals that tell
malignant B cells to multiply and spread
uncontrollably.7
IMBRUVICA is being studied alone and in combination with other
treatments in several blood cancers. Over 5,100 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 60 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 to treat people with:
- Chronic lymphocytic leukemia (CLL) who have received at least
one prior therapy
- Chronic lymphocytic leukemia (CLL) with 17p deletion
- Waldenstrom'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,
neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain,
bruising, nausea, upper respiratory tract infection, and rash.
Seven percent of patients receiving IMBRUVICA®
discontinued treatment due to adverse events.
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.
For additional important safety information, please see Full
Prescribing Information
at 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
product candidates, and our plans, objectives, expectations and
intentions. Because these statements apply to future events, they
are subject to risks and uncertainties. When used in this
announcement, the words "anticipate", "believe", "estimate",
"expect", "expectation", "goal", "should", "would", "project",
"plan", "predict", "intend", "target" and similar expressions are
intended to identify such forward-looking statements. These
forward-looking statements are based on information currently
available to us and are subject to a number of risks, uncertainties
and other factors that could cause our actual results, performance,
expected liquidity or achievements to differ materially from those
projected in, or implied by, these forward-looking statements.
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
ability to protect and enforce our intellectual property rights and
to operate without infringing upon the proprietary rights of third
parties. Although we believe that the expectations reflected in the
forward-looking statements are reasonable, we cannot guarantee
future results, performance or achievements and no assurance can be
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] IMS Database [Data on File]
[2] American Cancer Society. What are the key statistics for
chronic lymphocytic leukemia? Available
from: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics.
Accessed April 2015.
[3] Veliz M, Pinilla-Ibarz J. Cancer Control. Treatment of
Relapsed or Refractory Chronic Lymphocytic Leukemia. January
2012, Vol. 19, No. 1.
[4] NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkins
Lymphomas. Version 1.2014.
http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf.
Accessed April 2015.
[5] Schnaiter A, Stilgenbauer S. 17p deletion in chronic
lymphocytic leukemia: risk stratification and therapeutic approach.
Hematol Oncol Clin North Am. 2013;27:289-301.
[6] Stilgenbauer S, Zenz T. Understanding and managing ultra
high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol
Educ Program. 2010;2010: 481-8.
[7] IMBRUVICA Prescribing Information, January
2015
[8] Genetics Home Reference. Isolated growth hormone deficiency.
Available at:
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed April 2015.
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SOURCE Pharmacyclics, Inc.