Data Presented at American Society of Hematology from Ibrutinib
Phase 1b/2 and Phase 2 Trials Suggest High and Durable Response in
Chronic Lymphocytic Leukemia
ATLANTA, Dec. 8, 2012 /PRNewswire/ -- Pharmacyclics, Inc.
(NASDAQ: PCYC) today announced follow-up results that its
investigational oral therapy ibrutinib (PCI-32765), as a single
agent, resulted in durable responses for patients over 65 years of
age with treatment-naive chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL) and for those with
relapsed/refractory (RR) or high-risk (HR) disease.
In a study of 116 patients, the overall response rate (ORR) was
68 percent in elderly treatment-naive (TN) patients with an
estimated 96 percent progression-free survival (PFS) rate at 26
months. In patients with RR CLL/SLL, including those with HR
disease, the ORR was 71 percent with an estimated PFS at 26 months
of 75 percent.
A second study in 40 patients with HR CLL treated with the
combination of ibrutinib and rituximab therapy reported an ORR of
83 percent, with 38 of the 40 patients continuing on therapy
without disease progression. Patients with HR disease have inferior
responses to standard chemo-immunotherapy and shorter rates of PFS
and OS.
These findings, from ongoing Phase 1b/2 and Phase 2 trials, were
presented in a press briefing today at the 54th annual
meeting of the American Society of Hematology in Atlanta, GA. CLL and SLL are common B-cell
non-Hodgkin lymphomas.
In describing the findings of the Phase 1b/2 ibrutinib
monotherapy trial, lead investigator John
C. Byrd, M.D., said, "We are very encouraged that these
results with ibrutinib continue to support the possibility that we
can address some of the critical unmet needs in CLL/SLL." Dr. Byrd
is the D. Warren Brown Chair of Leukemia Research and Director,
Division of Hematology at Ohio State
University Comprehensive Cancer Center — Arthur G. James
Cancer Hospital and Richard J. Solove Research Institute (OSUCCC —
James).
In his presentation, Dr. Byrd noted that current therapies have
a number of limitations in terms of how long they can be used in a
patient and their tolerability, especially in elderly patients.
"Further, virtually all patients relapse, and there are few salvage
regimens that produce durable remissions," he pointed out.
The Phase 2 trial, evaluating ibrutinib in combination with
rituximab, was led by Jan A. Burger,
M.D., Ph.D., associate professor, Department of Leukemia, Division
of Cancer Medicine, The University of
Texas MD Anderson Cancer Center, Houston, TX.
"We are very excited by the response rates we saw with
ibrutinib-rituximab combination therapy, and believe they emphasize
the need for rapid, further development of ibrutinib, especially
for patients with high-risk CLL/SLL," said Dr. Burger.
Studies and Findings
Oral presentation 189, The
Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib (PCI-32765)
promotes high response rate, durable remissions, and is tolerable
in treatment naive (TN) and relapsed or refractory (RR) chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
patients including patients with high-risk (HR) disease: New and
updated results of 116 patients in a phase Ib/II
study
John C. Byrd, M.D., The
Ohio State University, Columbus, OH
This presentation was based on findings from a Phase 1b/2,
multi-center trial with 116 patients with TN (n=31), RR (n=61) or
HR (n=24) CLL/SLL. Patients were treated with oral ibrutinib
monotherapy, either 420 mg or 840 mg daily. Patients with RR
disease had received at least two prior therapies; patients with HR
disease had relapsed within two years following
chemo-immunotherapy. The study objectives were to determine the
ORR, PFS, overall safety (OS), safety of the two dosing regimens
and pharmacokinetics/pharmacodynamics.
- The overall response rates were:
- 68 percent in TN patients, all of whom were over 65 years old,
after a median follow up of 20.3 months
- 71 percent in patients with RR disease, including patients with
HR CLL/SLL, after a median follow up of 15.7 months
- The estimated PFS at 26 months is 96 percent for patients over
65 years of age with TN CLL and 75 percent for those with RR/HR
disease
- Estimated OS at 26 months is 96 percent in TN patients and 83
percent in patients with RR/HR disease
Responses were independent of high-risk clinical or genetic
features, such as a deletion of part of chromosome 17 (del17p).
Most adverse events (AEs) were Grade 1 or 2 in severity, with
the most common attributed to ibrutinib being diarrhea, fatigue,
nausea and rash. Adverse hematologic events were relatively
infrequent. In patients with cytopenia (low blood cell counts) at
the beginning of the study, sustained improvements of platelet
counts (78 percent) and hemoglobin (82 percent) were seen after
treatment. There was no evidence of cumulative toxicity or
long-term safety concerns.
Oral presentation 187, The BTK inhibitor ibrutinib
(PCI-32765) in combination with rituximab is well tolerated and
displays profound activity in high-risk chronic lymphocytic
leukemia (CLL) patients
Jan A.
Burger, M.D., Ph.D., MD Anderson Cancer Center, Houston, TX
This presentation was based on findings from a Phase 2,
single-center trial with 40 patients with HR CLL treated with 420
mg/day ibrutinib in combination with rituximab, a current standard
CLL therapy. Patients with HR disease were previously treated and
had one of the following characteristics: deletion of a part of
chromosome 17 (del17p), which is associated with poorer treatment
outcomes; a gene mutation called TP53; del11q, another partial
chromosome deletion associated with poorer outcomes; or a short
remission duration (less than three years) after first-line
chemo-immunotherapy.
The results after a follow-up of three to six months are:
- The ORR was 83 percent
- 38 of 40 patients continue on therapy without disease
progression
- 95 percent of all patients and 90 percent of patients with
del17p had not progressed
- There was a large and rapid reduction in lymph node and spleen
sizes, with 84 percent of patients (26/31) experiencing more than a
50 percent decrease in lymph node size
- Treatment was well tolerated overall, with Grade 3 or Grade 4
toxicities infrequent and transient in nature, including febrile
neutropenia (fever with low white blood cell count), anemia,
mucositis and pneumonia, in this clinical study
"We believe the updated findings from these two trials further
affirm the possibilities of ibrutinib," said Bob Duggan, CEO and Chairman of the Board of
Directors of Pharmacyclics. "We look forward to continuing our
clinical development program for this therapy, and hope it can help
us in achieving Pharmacyclics' mission of improving the quality and
duration of life for patients with oncologic diseases."
About Ibrutinib
Ibrutinib was designed to specifically
target and selectively inhibit an enzyme called Bruton's tyrosine
kinase (BTK). BTK is a key mediator of at least three critical
B-cell pro-survival mechanisms occurring in parallel – regulating
B-cell apoptosis, cell adhesion, and lymphocyte migration and
homing. Data are consistent with a mechanistic model whereby
ibrutinib blocks BCR signaling, which drives cells into apoptosis
and/or disrupts cell migration and adherence to tumor-protective
microenvironments.
The effectiveness of ibrutinib alone or in combination with
other treatments is being studied in several B-cell malignancies,
including CLL/SLL, relapsed/refractory mantle cell lymphoma,
diffuse large B-cell lymphoma, follicular lymphoma and multiple
myeloma. A comprehensive late stage Phase 2 and 3 program is under
way.
Conference Call and Webcast Details
Pharmacyclics will
be holding a conference call on Wednesday,
December 12, 2012 at 8:30 AM
ET. To participate in the conference call, please dial
1-877-407-0778 for domestic callers and 1-201-689-8565 for
international callers. To access the live audio broadcast or the
subsequent archived recording, log on to
http://ir.pharmacyclics.com/events.cfm. The archived version of the
webcast will be available for 30 days on the Investor Relations
section of the company's website at www.pharmacyclics.com.
About the Pharmacyclics and Janssen
Collaboration
Pharmacyclics and Janssen Biotech, Inc.
entered into a worldwide collaboration on December 8, 2011, to develop and commercialize
ibrutinib. Following regulatory approval, Pharmacyclics and Janssen
will co-commercialize ibrutinib. Each company will lead development
for specific indications as stipulated in a global development
plan.
About Pharmacyclics
Pharmacyclics® is a
clinical-stage 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 medial
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.
Presently, Pharmacyclics has three product candidates in
clinical development and several preclinical molecules in lead
optimization. We are committed to high standards of ethics,
scientific rigor, and operational efficiency as we move each of
these programs to viable commercialization.
The Company 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
http://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 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 future events, they are subject to risks and
uncertainties. When used in this announcement, the words
"anticipate", "believe", "estimate", "expect", "expectation",
"should", "would", "project", "plan", "predict", "intend" and
similar expressions are intended to identify such forward-looking
statements. These forward-looking statements are based on
information currently available to us and are subject to a number
of risks, uncertainties and other factors that could cause our
actual results, performance or achievements to differ materially
from those projected in, or implied by, these forward-looking
statements. Factors 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 heavily on collaboration with third
parties, and our ability to protect and enforce our intellectual
property rights and to operate without infringing 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 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 annual report
on Form 10-K 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.
Note: Data in this release correspond to ASH Abstracts 189
and 187.
SOURCE Pharmacyclics, Inc.