Ibrutinib Frontline Chronic Lymphocytic Leukemia Study Results Published in
The Lancet Oncology
-- Estimated progression-free survival at 24 months was 96.3 percent in this
Phase 1b/2 trial--
SUNNYVALE, Calif., Dec. 9, 2013
SUNNYVALE,Calif., Dec. 9, 2013 /PRNewswire/ --Pharmacyclics, Inc. (NASDAQ:
PCYC) today announced that The Lancet Oncology published results of a study
evaluating ibrutinib in previously untreated elderly patients with chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The Phase 1b/2
open-label, multicenter study evaluated 31 patients, 65 years of age and older
with CLL or SLL. The primary endpoint of the study was safety, as assessed by
the frequency and severity of adverse events (AEs), while the secondary
objectives assessed the clinical activity of single agent ibrutinib. Only one
patient out of the 31 enrolled in this cohort has had progression of disease.
After a median follow-up of 22.1 months (range, 18.4-23.2), the overall
response rate (ORR) for patients was 71 percent (95% CI, 52-86), which
included 55 percent partial response, 3 percent nodular partial response and
13 percent complete response. An additional 13 percent of patients achived a
partial response with lymphocytosis. The median time to initial response was
1.9 months (range, 1.5-7.4); the median time to best response and complete
response were 5.9 months (range, 1.8-22.1) and 12.0 months (range, 7.1-15.6),
Across all patients, the estimated progression-free survival (PFS) and overall
survival at 24 months were 96.3 percent (95% CI, 76.5-99.5) and 96.6 percent
(95% CI, 77.9-99.5), respectively.
"Older patients with CLL and SLL are at particularly high risk, and the
standard of care therapies for these patients can often lead to significant
and burdensome complications," said lead author Susan O'Brien, M.D.,
Department of Leukemia, Division of Cancer Medicine, The University of Texas
MD Anderson Cancer Center. "There is a need for new treatment options, and we
are encouraged by the high response rate and tolerability seen with ibrutinib
as a first line therapy."
The majority of AEs that occurred were mild and Grade 1 or 2 in severity.
Diarrhea was seen in 21 of 31 patients (68%) and was grade 1 in 14 of 31
patients (45%), grade 2 in three patients (10%), and grade 3 in four patients
(13%). There were no episodes of grade 4 diarrhea. Nausea was predominantly
grade 1 (12 of 31 patients; 39%), with a maximum grade of 2 (three of 31
patients (10%). Fatigue was seen in 10 of the 31 patients (32%), including
five patients (16%) with grade 1, four (13%) with grade 2, and one (3%) with
grade 3. Grade 3 infections were noted in three of the 31 patients (10%); no
grade 4 or 5 infections were observed. There was one grade 3 neutropaenia and
one grade 4 thrombocytopaenia. Two patients discontinued treatment for adverse
events that included grade 3 fatigue in one patient and grade 2 viral
infection in a second patient.
In this study, response to ibrutinib was assessed on the basis of the
International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for
CLL patients, with the exception that lymphocytosis was not a sole criterion
for disease progression. Response in SLL patients was assessed by
International Working Group for non-Hodgkin lymphoma (IWGNHL) 2007 criteria.
Earlier data from this study were presented at the annual meeting of the
American Society of Hematology in December 2012 and the American Society of
Clinical Oncology in June 2012. The study was sponsored by Pharmacyclics, Inc.
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™ (ibrutinib) 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.
To date, nine Phase III trials have been initiated with IMBRUVICA and a total
of 37 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.
For more information, visit www.IMBRUVICA.com.
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 markets IMBRUVICA and has two other 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.
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 ibrutinib in patients requiring antiplatelet or
anticoagulant therapies and the benefit-risk of withholding ibrutinib 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
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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, or U.S. Medical Information, Pharmacyclics, 877-877-3536
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