Pharmacyclics Files Supplemental New Drug Application for IMBRUVICA with Phase
III CLL Study Data
SUNNYVALE, Calif., April 8, 2014
SUNNYVALE, Calif., April 8, 2014 /PRNewswire/ --Pharmacyclics, Inc. (NASDAQ:
PCYC) today announced that it has submitted a supplemental New Drug
Application (sNDA) to the U.S. Food and Drug Administration (FDA), based on
data from the randomized, multi-center, open-label Phase III RESONATE^TM
study, PCYC-1112, a head-to-head comparison of single agent IMBRUVICA^TM
(ibrutinib) versus ofatumumab in 391 patients with chronic lymphocytic
leukemia (CLL) or small lymphocytic lymphoma (SLL), who had received at least
one prior therapy. IMBRUVICA is being jointly developed and commercialized by
Pharmacyclics and Janssen Biotech, Inc.
At a planned interim analysis in January 2014, the results of the RESONATE
study demonstrated a statistically significant improvement in progression-free
survival, the primary endpoint of the study, in patients treated with
IMBRUVICA. Further, patients in the IMBRUVICA arm also showed a statistically
significant improvement in overall survival, a key secondary endpoint of the
trial. The safety profile of IMBRUVICA was acceptable and showed a favorable
risk benefit profile. Data from this study will be discussed in a presentation
at the 50^th annual meeting of the American Society of Clinical Oncology in
Chicago, May 30 – June 3, 2014.
"This supplemental new drug application in previously treated CLL patients is
our first Phase III submission to the FDA seeking full approval for the use of
IMBRUVICA. It is another major milestone in our clinical development plan,
which currently includes 10 Phase III studies," said Bob Duggan, CEO and
Chairman of the Board of Pharmacyclics. "Our company's mission is to serve as
an ally to patients. In the RESONATE study, single agent IMBRUVICA provided a
significant benefit for patients with CLL. We look forward to working with the
FDA as they review the data from this Phase III study."
The FDA granted an accelerated approval for IMBRUVICA as a single agent for
the treatment of patients with MCL or CLL, who have received at least one
prior therapy. The accelerated approval for these indications was based on the
overall response rate (ORR) of patients in the Phase II clinical studies of
PCYC-1102 and PCYC-1104. An improvement in survival or disease-related
symptoms was not established in these studies. IMBRUVICA is the first
once-daily, single-agent, oral kinase inhibitor for patients with MCL or CLL
who have received one prior therapy.
CLL is a slow-growing blood cancer of the white blood cells (lymphocytes),
most commonly B-cells. CLL is the most common adult leukemia. Approximately
16,000 patients in the U.S. are diagnosed each year with CLL. The prevalence
of CLL is approximately 114,500 in the U.S. CLL is a chronic disease that
predominantly occurs in the elderly and the average age of diagnosis is 72.The
five-year survival is approximately 82 percent.
MCL is also a blood cancer; it is an aggressive type of B-cell non-Hodgkin
lymphoma (NHL) that usually occurs in older adults. The disease typically
involves the lymph nodes, but can spread to other tissues, such as bone
marrow, liver, spleen, and gastrointestinal tract. The prevalence of MCL is
approximately 11,300 in the U.S. and patients survive an average of five
CLL and MCL are both classified as orphan or rare diseases, defined as agents
which affect fewer than 200,000 Americans. ^ Patients commonly receive
multiple lines of treatment over the course of their disease.
IMBRUVICA 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.
The FDA's accelerated approval of these indications was based on the overall
response rate of patients in the Phase II clinical trials of PCYC-1102 and
PCYC-1104. Improvements in survival or disease-related symptoms were not
established in these studies.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent of patients with MCL and 6% of patients with CLL had
Grade 3 or higher 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 IMBRUVIC 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 or greater 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 (5.4%), 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 (6.3%), sinusitis (6%),
skin infection (6%), dehydration (6.4%), 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.
SPECIAL POPULATIONS - Hepatic Impairment - Avoid use in patients with baseline
For the full prescribing information, visit
Access to IMBRUVICA
Patients who are prescribed IMBRUVICA can receive access support through
several distinct programs:
oThe YOU&i Start™ program enables eligible patients who have been
prescribed IMBRUVICA for an FDA-approved indication and are experiencing
insurance coverage delays to access free product for a limited period of
time, if they meet certain requirements. In addition, our YOU&i Access
service center is set up to help patients ensure that all access-related
administration is properly handled.
oThe YOU&i Access™ Instant Savings Program helps commercially insured
patients who have difficulties with out-of-pocket expenses for IMBRUVICA.
Eligible patients may receive support to reduce their monthly
out-of-pocket costs to $25.
oPatients who are deemed uninsured and eligible, and who qualify based on
financial need, can access IMBRUVICA through the Johnson & Johnson Patient
Assistance Foundation (JJPAF), an independent non-profit organization to
which Pharmacyclics makes donations.
oPharmacyclics will also support third party foundations, organizations and
other efforts to help patients in need get access to appropriate care.
More information about these comprehensive patient access programs is
accessible at 1-877-877-3536 or at www.IMBRUVICA.com.
IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma
or chronic lymphocytic leukemia who have received at least one prior
therapy.^1 For more information about IMBRUVICA, including the full
prescribing information, please visit www.IMBRUVICA.com. IMBRUVICA is a first
in class, oral therapy and is a new agent that inhibits a protein called
Bruton's tyrosine kinase (BTK).^1 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.^8,9,10 IMBRUVICA blocks signals that tell
malignant B cells to multiply and spread uncontrollably.^1,11 It 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, nine Phase III trials have been initiated with ibrutinib and a total
of 39 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.
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,
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achieve market acceptance of any of our product candidates, for which we rely
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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
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SOURCE Pharmacyclics, Inc.
Contact: Media, Manisha Pai, Senior Director, Public Relations and Corporate
Communications, Phone: 408-215-3720 or Cell: 617-510-9193, or Investors,
Ramses Erdtmann, Senior Vice President, Investor Relations, Phone:
408-215-3325, U.S. Medical Information, Pharmacyclics877-877-3536
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