IMBRUVICA® (ibrutinib) Shows Durable, Long-Term Responses for Patients with
SUNNYVALE, Calif., May 31, 2014
SUNNYVALE, Calif., May 31, 2014 /PRNewswire/ --Pharmacyclics, Inc. (NASDAQ:
PCYC) announced today that IMBRUVICA®^(ibrutinib) will be featured in an oral
presentation highlighting long-term responses to treatment, with up to three
years of follow up in 132 patients with treatment naive or relapsed/refractory
chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The
results from this study will be presented at the 50^th Annual Meeting of the
American Society of Clinical Oncology (ASCO) on June 2, 2014, at 11:33 a.m.
CT. This release corresponds to abstract 7014. IMBRUVICA is being jointly
developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
In the treatment naive group, 31 CLL patients, aged 65 years or older,
received single agent IMBRUVICA once daily and were followed in the study for
a median time of 32.1 months. The Overall Response Rate, as assessed by the
Investigator, was 87% (Complete Response (CR) 13%, nodular PR (nPR) 3%,
partial response (PR) 65%, partial response with lymphocytosis (PRL) 6%). Only
one patient had progressive disease during the median follow up of 32.1 months
and the progression-free survival (PFS) at 30 months was 96%. The overall
survival (OS) for these patients at 30 months was 97%.
In the relapsed/refractory group, 101 patients with CLL/SLL (median of 4 prior
therapies, 57% Rai stage III or IV (indicative of high risk CLL patients), 69%
of patients had the high-risk characteristics of deletion of short arm of
chromosome 17 or 11 (del 17p or del 11q)) received single-agent IMBRUIVCA once
daily and were followed in the study for a median time of 26.6 months. Overall
90% of patients achieved a best response of PR-L or higher. For patients
without del17p or del11q, the estimated PFS was 89% at 30 months. The median
PFS for del17p patients was 28.1 months and for patients with del11q the
median PFS had not been reached and was estimated to be 74% at 30 months. The
estimated OS for these relapsed or refractory patients was 79.9%.
Following all the patients in this study for up to 3 years, the percentage of
patients with AEs as a primary reason leading to discontinuation decreased
over time, with 8% in the first year, 2% in the second year and 3% in the
third year. Similarly, the percentage of who experienced a death on study
decreased over time, with 5% in the first year, 4% in the second year and 3%
in the third year.
"These results suggest responses to IMBRUVICA are exceptionally durable in
patients with CLL with a median observation period past 30 months," said Dr.
Susan O'Brien*, Department of Leukemia, Division of Cancer Medicine, MD
Anderson Cancer Center, Houston, TX. "IMBRUVICA is very well tolerated. We are
especially encouraged to see that patients showed durable responses regardless
of their treatment history."
"Our company's mission is to serve as an ally to patients by improving their
quality and duration of life," said Bob Duggan, CEO and Chairman of the Board
for Pharmacyclics. "The long-term follow-up data in this clinical study shows
a continuation of benefits for CLL patients 3 years after treatment initiation
and a decrease in adverse events leading to discontinuation. We are very
excited about these outstanding achievements and it is with great confidence
that we continue to expand the already broad clinical development of
CLL is a slow-growing blood cancer of white blood cells called lymphocytes,
most commonly B cells.^^1 CLL is the most common adult leukemia in the Western
world and predominantly a disease of the elderly with a median age at
diagnosis of 72.^2 As this orphan disease frequently progresses after front
line therapy; patients are faced with fewer treatment options and are often
prescribed multiple lines of therapy as they relapse or become resistant to
IMBRUVICA is a first in class, oral therapy that inhibits a protein called
Bruton's tyrosine kinase (BTK). BTK is a key signaling molecule of the B-cell
receptor signaling complex that plays an important role in the survival and
spread of malignant B cells. IMBRUVICA blocks signals that tell malignant B
cells to multiply and spread uncontrollably.
The FDA approved IMBRUVICA for previously treatedMCL on November 12, 2013 and
for previously treated CLL on February 12, 2014. The FDA's accelerated
approval for these indications was based on overall response rate of patients
in the phase II clinical studies of PCYC-1102 and PCYC-1104. IMBRUVICA is one
of the first medicines to file for FDA approval via the new Breakthrough
Therapy Designation pathway, enabling Pharmacyclics to rapidly bring this
medicine to patients in need.
To date, 11 Phase III trials have been initiated with IMBRUVICA and a total of
45 trials are currently registered on www.clinicaltrials.gov. Janssen and
Pharmacyclics entered a collaboration and license agreement in December 2011
to co-develop and co-commercialize IMBRUVICA .
IMBRUVICA™ (ibrutinib) is indicated for the treatment of:
oPatients with mantle cell lymphoma (MCL) who have received at least one
oPatients with chronic lymphocytic leukemia (CLL) who have received at
least one prior therapy.
These indications are based on overall response rate. Improvements in survival
or disease-related symptoms have not been established.
The following safety information is described in the package insert for the
use of IMBRUVICA.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage - Five percent of patients with MCL and 6% of patients with CLL
had>/=Grade 3 bleeding events (subdural hematoma, ecchymoses,
gastrointestinal bleeding, and hematuria). Overall, bleeding events including
bruising of any grade occurred in 48% of patients with MCL treated with 560 mg
daily and 63% of patients with CLL treated at 420 mg daily.
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. At least 25% of patients with MCL and 35% of patients with CLL had
infections>/= Grade 3 according to NCI Common Terminology Criteria for
Adverse Events (CTCAE). Monitor patients for fever and infections and evaluate
Myelosuppression - Treatment-emergent Grade 3 or 4 cytopenias were reported in
41% of patients with MCL and 35% of patients with CLL. These included
neutropenia (29%), thrombocytopenia (17%) and anemia (9%) in patients with MCL
and neutropenia (27%) and thrombocytopenia (10%) in patients with CLL. Monitor
complete blood counts monthly.
Renal Toxicity - Fatal and serious cases of renal failure have occurred with
IMBRUVICA® therapy. Treatment-emergent increases in creatinine levels up to
1.5 times the upper limit of normal occurred in 67% of patients with MCL and
23% of patients with CLL. Increases in creatinine 1.5 to 3 times the upper
limit of normal occurred in 9% of patients with MCL and 4% of patients with
CLL. Periodically monitor creatinine levels. Maintain hydration.
Second Primary Malignancies - Other malignancies have occurred in 5% of
patients with MCL and 10% of patients with CLL who have been treated with
IMBRUVICA®. Four percent of patients with MCL, had skin cancers and 1% had
other carcinomas. Eight percent of patients with CLL had skin cancers and 2%
had other carcinomas.
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 -
MCL: The most commonly occurring adverse reactions (>/= 20%) in the clinical
trial were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue
(41%), musculoskeletal pain (37%), peripheral edema (35%), upper respiratory
tract infection (34%), nausea (31%), bruising (30%), dyspnea (27%),
constipation (25%), rash (25%), abdominal pain (24%), vomiting (23%), and
decreased appetite (21%).
*Treatment-emergent decreases (all grades) of platelets (57%), neutrophils
(47%) and hemoglobin (41%) were based on laboratory measurements and adverse
The most common Grade 3 or 4 non-hematological adverse reactions (>/= 5%) were
pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%),
fatigue (5%), and skin infections (5%). Treatment-emergent Grade 3 or 4
cytopenias were reported in 41% of patients.
Ten patients (9%) discontinued treatment due to adverse reactions in the trial
(N=111). The most frequent adverse reaction leading to treatment
discontinuation was subdural hematoma (1.8%). Adverse reactions leading to
dose reduction occurred in 14% of patients.
CLL: The most commonly occurring adverse reactions (>/= 20%) in the clinical
trial were thrombocytopenia*, diarrhea (63%), bruising (54%), neutropenia*,
anemia*, upper respiratory tract infection (48%), fatigue (31%),
musculoskeletal pain (27%), rash (27%), pyrexia (25%), constipation (23%),
peripheral edema (23%), arthralgia (23%), nausea (21%), stomatitis (21%),
sinusitis (21%), and dizziness (21%).
*Treatment-emergent decreases (all grades) of platelets (71%), neutrophils
(54%) and hemoglobin (44%) were based on laboratory measurements per IWCLL
criteria and adverse reactions.
The most common Grade 3 or 4 non-hematological adverse reactions (>/= 5%) were
pneumonia (8%), hypertension (8%), atrial fibrillation (6%), sinusitis (6%),
skin infection (6%), dehydration (6%), and musculoskeletal pain (6%).
Treatment-emergent Grade 3 or 4 cytopenias were reported in 35% of patients.
Five patients (10%) discontinued treatment due to adverse reactions in the
trial (N=48). These included 3 patients (6%) with infections and 2 patients
(4%) with subdural hematomas. Adverse reactions leading to dose reduction
occurred in 13% of patients.
CYP3A Inhibitors - Avoid concomitant administration with strong or moderate
inhibitors of CYP3A. If a moderate CYP3A inhibitor must be used, reduce the
CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.
Hepatic Impairment - Avoid use in patients with baseline hepatic impairment.
For the full prescribing information, visit
Pharmacyclics^® is a biopharmaceutical company focused on developing and
commercializing innovative small-molecule drugs for the treatment of cancer
and immune mediated diseases. Our mission and goal 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 healthcare needs; and to identify and control
promising product candidates based on scientific development and
administrational expertise, develop our products in a rapid, cost-efficient
manner and pursue commercialization and/or development partners when and where
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 viable
Pharmacyclics is headquartered in Sunnyvale, California and is listed on
NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances
science to improve human healthcare visit us at www.pharmacyclics.com.
NOTE: This announcement may contain forward-looking statements made in
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^1 American Cancer Society. "Leukemia--Chronic Lymphocytic".
Accessed April 2014.
^2 Decision Resources estimate 2013.
^3 Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic
lymphocytic leukemia. Cancer Control. 2012 Jan;19(1):37-53.
*Dr. O'Brien has served as an unpaid advisor to both Pharmacyclics and Janssen
in developing the compound ibrutinib. Dr. O'Brien does not have a financial
interest in either company.
SOURCE Pharmacyclics, Inc.
Contact: Ramses Erdtmann, EVP of Corporate Affairs, Phone: 408-215-3325, or
Thomas Butler, Manager Investor Relations, Phone: 408-215-3683, or U.S.
Medical Information, Pharmacyclics: 855-ibrutinib [(855)-427-8846],
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