Independent Data Monitoring Committee recommends Phase III study of IMBRUVICA™
(ibrutinib) versus ofatumumab be stopped early based on statistically
significant improvement in progression free survival and overall survival
SUNNYVALE, Calif., Jan. 7, 2014
SUNNYVALE, Calif., Jan. 7, 2014 /PRNewswire/ --Pharmacyclics, Inc. (NASDAQ:
PCYC) today announced that an Independent Data Monitoring Committee (IDMC)
unanimously recommended that the Phase III RESONATE study, PCYC-1112-CA, a
head-to-head comparison of IMBRUVICA^TM (ibrutinib) versus ofatumumab, be
stopped early because the primary and a key secondary endpoint of the study
have been met. At the planned interim analysis, the Phase III RESONATE study
demonstrated that IMBRUVICA showed a statistically significant improvement in
progression-free survival (the primary endpoint of the study, which was
evaluated by an independent review committee) in patients with relapsed or
refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL). Further, IMBRUVICA showed statistically significant improvement in
overall survival (a key secondary endpoint of the trial). The safety profile
of IMBRUVICA was acceptable and consistent with prior clinical experience.
The IDMC recommended that the sponsor provide access to IMBRUVICA for
subjects on the ofatumumab arm.
"We are very pleased with the vigilance and professional expertise that our
IDMC exercised in monitoring this study. The results seen at the interim
analysis of the RESONATE trial are robust and consistent," said Fong Clow,
Sc. D, Senior Vice President of Biometrics at Pharmacyclics.
Pharmacyclics has informed the U.S. Food and Drug Administration (FDA) of the
recommendations of the IDMC. Similarily, Janssen, the co-developer of
IMBRUVICA, has informed the European Medicines Agency (EMA). Both companies
are engaging in a dialogue with the Health Authorities to define the next
regulatory steps and anticipate providing a comprehensive RESONATE study
report to them within the coming months.
"I am tremendously proud of the accomplishment of the Pharmacyclics team for
their effort and execution as well as the collaboration with the clinical
sites toward this high quality study. This collaboration resulted in
expeditious enrollment, and rapid data collection and analysis. This global
study involving 391 patients was conducted at more than 70 clinical sites in
10 countries," said Maria Fardis, PhD, Chief of Oncology Operations and
Alliances at Pharmacyclics.
"We express our appreciation to the patients, the investigators and the entire
Pharmacyclics and Janssen teams for overcoming the barriers and challenges
associated with this exciting scientific outcome," said Robert Duggan, Chief
Executive Officer and Chairman of the Board of Pharmacyclics.
The company anticipates that the detailed data analysis from this RESONATE
Phase III study will be presented at an upcoming oncology conference.
RESONATE is a randomized, multicenter, open-label Phase III study of single
agent IMBRUVICA (ibrutinib) versus single agent ofatumumab in patients with
relapsed or refactory CLL or relapsed or refractory SLL with measurable nodal
disease and who were not eligible for treatment with purine analog-based
therapy. The study enrolled 391 patients who had received at least one prior
therapy. Patients were randomized to receive 420 mg of IMBRUVICA orally once
daily or intravenous doses of ofatumumab over the course of 24 weeks until
disease progression or unacceptable toxicity. Patients randomized to the
ofatumumab arm who experienced disease progression were evaluable for
consideration of subsequent IMBRUVICA therapy.
CLL, a B-cell malignancy, is a slow-growing blood cancer of the white blood
cells (lymphocytes), most commonly from B-cells. CLL is the second most common
adult leukemia. Approximately 16,000 patients in the U.S. are diagnosed each
year with CLL. The prevalence of CLL is approximately 113,000 in the U.S. CLL
is a chronic disease that predominantly occurs in the elderly with a five-year
survival of approximately 82 percent.Patients commonly receive multiple lines
of treatment over the course of their disease. When cancer cells are located
mostly in the lymph nodes, the disease is called SLL. CLL and SLL are
considered to be different manifestations of the same underlying disease; they
share similarities in signs and symptoms, genetic features, disease
progression and treatment.
IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma
who have received at least one prior therapy. This indication is based on
overall response rate (ORR). An improvement in survival or disease-related
symptoms has not been established. 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). BTK is a key signaling molecule
of the B-cell receptor signaling complex that plays an important role in the
survival of malignant B cells. IMBRUVICA blocks signals that tell malignant B
cells to grow and divide uncontrollably. It is one of the first medicines to
receive FDA approval via the new Breakthrough Therapy Designation pathway,
enabling Pharmacyclics to rapidly bring this medicine to patients in need.
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 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 appropriate.
Pharmacyclics 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 commercialization.
To date, 9 Phase III trials have been initiated with IMBRUVICA (ibrutinib) and
a total of 38 trials are currently registered on www.clinicaltrials.gov.
Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license
agreement in December 2011 to co-develop and co-commercialize IMBRUVICA.
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.
The following safety information is described in the package insert for the
use of IMBRUVICA in patients with mantle cell lymphoma who have received at
least one prior therapy:
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage - 5% of patients with MCL had ≥ Grade 3 bleeding events (subdural
hematoma, gastrointestinal bleeding, and hematuria). Bleeding events including
bruising of any grade occurred in 48% of patients with MCL treated with 560 mg
daily. The mechanism for the bleeding events is not well understood. Consider
the benefit-risk of IMBRUVICA in patients requiring antiplatelet or
anticoagulant therapies and 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. At least 25% of
patients with MCL had infections ≥ Grade 3, according to NCI Common
Terminology Criteria for Adverse Events (CTCAE). Monitor patients for fever
and infections and evaluate promptly.
Myelosuppression - Treatment-emergent Grade 3 or 4 cytopenias were reported in
41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and
anemia (9%). Monitor complete blood counts monthly.
Renal Toxicity - Fatal and serious cases of renal failure have occurred.
Treatment-emergent increases in creatinine levels up to 1.5 times the upper
limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper
limit of normal in 9% of patients. Periodically monitor creatinine levels.
Second Primary Malignancies - Other malignancies (5%) have occurred in
patients with MCL who have been treated with IMBRUVICA, including skin cancers
(4%) and other carcinomas (1%).
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.
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
*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, 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.
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
Because everyone is different, it is not possible to predict what side effects
any one patient will have. Patients with questions or concerns about side
effects should talk to their doctor.
Report side effects to the FDA at (800) FDA-1088
For more information please read the IMBRUVICA Full Prescribing Information at
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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that may cause such a difference include, without limitation, our need for
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financing, the safety and/or efficacy results of clinical trials of our
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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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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
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forward-looking statements. For more information about the risks and
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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.
SOURCE Pharmacyclics, Inc.
Contact: Media, Manisha Pai, Senior Director, Public Relations and Corporate
Communications, 408-215-3720; or Investors, Ramses Erdtmann, Senior Vice
President, Investor Relations, 408-215-3325; or U.S. Medical Information,
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