IMBRUVICA® (ibrutinib) Combination with anti CD20 Antibody Shows Compelling
Results in Heavily Pretreated Patients with CLL and Related Diseases
SUNNYVALE, Calif., May 31, 2014
SUNNYVALE, Calif., May 31, 2014 /PRNewswire/ --Pharmacyclics, Inc. (NASDAQ:
PCYC) announced today that IMBRUVICA®(ibrutinib) in combination with the
anti-CD20 antibody, ofatumumab, showed a Kaplan Meier estimate of continued
clinical response at 18 months of 82.5% in heavily pre-treated patients with
chronic lymphoma leukemia (CLL), small lymphocytic leukemia (SLL),
prolymphocytic leukemia (PLL) and Richters Transformation (RT). The median
duration of response for all dosing schedules in this study was not reached.
The results from this study will be presented at the 50^th Annual Meeting of
the American Society of Clinical Oncology (ASCO) today. This release
corresponds to abstract 7009. IMBRUVICA is being jointly developed and
commercialized by Pharmacyclics and Janssen Biotech, Inc.
The study design consisted of three dosing cohorts, group 1 received one month
of IMBRUVICA monotherapy followed by IMBRUVICA and ofatumumab in combination
thereafter, group 2 received IMBRUVICA and ofatumumab in combination from the
outset, and group 3 received two months of ofatumumab monotherapy followed by
IMBRUVICA and ofatumumab thereafter. Seventy-one (71) patients with
relapsed/refractory CLL/SLL/PLL and RT, with a median of 3 prior therapies,
were enrolled in the study (27,20, and 24 in groups 1,2, and 3 respectively).
Sixty-one percent (61%) of patients had RAI stage III/IV and were considered
high risk, 44% had deletion of the short arm of chromosome 17 (del17p), and
31% a deletion of the short arm of chromosome 11 (del11q), genetic mutations
typically associated with poor prognosis.
The overall response (including complete, partial and partial responses with
lymphocytosis) in CLL/SLL/PLL patients was 100%, 84%, and 75% in groups 1, 2
and 3 respectively, which were achieved within a median of 4.6 months during
the study. At study end 90% (52 of 58) of responders were progression free
with follow up of 16, 12 and 11 months for groups 1, 2 and 3 respectively. At
12 months, the PFS was 89%, 85%, and 75% in groups 1,2, and 3.
The adverse events (AEs) for all 3 cohorts combined were mostly grade 1 or 2
AEs. The most frequent events reported in 15% or more of patients were
diarrhea (68%, 5 cases of grade>/= 3), infusion related reaction ( 45%, 1
case of grade>/= 3), peripheral sensory neuropathy (42%, 2 cases of grade>/=
3), and stomatitis (37%, 2 cases of grade>/= 3).The grade 3 or higher AE,
reported in 15% or more of patients, was neutropenia (22.5%, 16 cases). Of all
71 patients, 6 patients had AEs leading to IMBRUVICA discontinuation.
"These IMBRUVICA results with an anti CD-20 antibody are compelling and
suggest that this combination is well tolerated and highly active," said Dr.
Samantha M. Jaglowski*, from the Ohio State University Comprehensive Cancer
Center – Arthur James Cancer Hospital & Richard J. Solove Research Institute.
"We are especially encouraged to see that with proper dosing sequence, heavily
pretreated CLL/SLL patients on this study have achieved 100% response rates
which are lasting over long durations."
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
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
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"intend", "target" and similar expressions are intended to identify such
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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
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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
transition report on Form 10-K for the six month period ended December 31,
2012 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.
^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. Jaglowski serves as an investigator on this clinical study. She has
served as an unpaid advisor to both Pharmacyclics and Janssen in developing
the compound ibrutinib. Dr. Jaglowski does not have a financial interest in
SOURCE Pharmacyclics, Inc.
Contact: Ramses Erdtmann, EVP of Corporate Affairs, Phone: 408-215-3325;
Thomas Butler, Manager Investor Relations, Phone: 408-215-3683; U.S. Medical
Information, Pharmacyclics: 855-ibrutinib [(855)-427-8846], email@example.com
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