Ibrutinib Three Year Follow-up of Single-Agent and Combination Study Results in Chronic Lymphocytic Leukemia

Beerse, Belgium (ots/PRNewswire) -

/NOT INTENDED FOR UK MEDIA/

Oral presentation (Abstract 7014) and poster session (Abstract
7009)

featured at the 50th annual meeting of the American Society of
Clinical Oncology

Three year follow-up data from the Phase 1b/2 PCYC-1102 trial of
monotherapy ibrutinib showed continued durable responses in patients
with treatment-naïve (TN) or relapsed or refractory chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL),
according to data from an analysis that will be discussed in an oral
presentation on Tuesday, June 3 at the American Society of Clinical
Oncology (ASCO) 50th annual meeting in Chicago, IL. Ibrutinib is an
investigational compound in the EU within a class of medicines called
Bruton's tyrosine kinase (BTK) inhibitors*.

Janssen announced the results today, which show ibrutinib
monotherapy continued to produce high overall response rates (ORR)
(78 percent for all treated patients, with the median duration of
response not achieved after almost 30 months and 25 months for
patients with del 17p). Moreover, the rate of Grade 3 or higher
adverse events (AEs) and serious adverse events or those leading to
hospitalisation decreased after one year on treatment.

*Ibrutinib is defined as an investigational compound as it is not
yet approved by any regulatory authority in the EU. On October 30,
2013, Janssen submitted a New Marketing Authorisation Application
(MAA) to the European Medicines Agency (EMA) for ibrutinib for the
treatment of adult patients with relapsed or refractory CLL/SLL or
relapsed or refractory mantle cell lymphoma (MCL). Ibrutinib is
marketed as IMBRUVICA(R) in the U.S., where it received approval from
the U.S. Food and Drug Administration (FDA) for the treatment of
patients with MCL who have received at least one prior therapy[1] and
for the treatment of patients with CLL who have received at least one
prior therapy.[2]

In a separate poster presentation to be discussed today, data
suggest the combination of single-agent ibrutinib administered orally
once-daily with ofatumumab, a CD20-directed cytolytic monoclonal
antibody administered intravenously, is tolerable in patients with
previously treated relapsed or refractory CLL/SLL.

In 2011, Janssen and Pharmacyclics Inc. entered into an agreement
to jointly develop and commercialise ibrutinib.

Three Year Follow-up of Single Agent Ibrutinib in Phase 1b/2 Trial

Three year follow-up from the initial Phase 1b/2 PCYC-1102 trial
of single-agent ibrutinib showed continued durable responses in
patients with treatment-naïve (TN) (n=31) or relapsed or refractory
CLL or SLL (n=101). Ibrutinib was associated with a 78 percent ORR,
with durable responses regardless of prior treatment history (83.9
percent in treatment-naïve patients, 76.2 percent in relapsed or
refractory patients, 55.9 percent in relapsed or refractory patients
with a deletion of the short arm of chromosome 17 [del 17p]). In
addition, five patients with relapsed or refractory CLL and two with
del 17p achieved a partial response (PR) with lymphocytosis as best
response. Patients received either single-agent ibrutinib once-daily
at either 420 mg or 840 mg daily. ORR was assessed based on
International Working Committee on Chronic Lymphocytic Leukemia
(IWCLL) criteria. The median time on study was 29.4 months (range,
0.7-38.1 months).

The median duration of response was not achieved for the full set
of patients (n=132) evaluated for the analysis. For relapsed or
refractory patients with del 17p, the median duration of response was
25 months (range 4.8-34.3 months).

"These results suggest significantly extended response to
ibrutinib in patients with CLL three years after starting treatment,"
said Professor Ulrich Jäger, Medical University of Vienna, Department
of Medicine, Division of Haematology and Hemostaseology. "We are
especially encouraged to see that patients showed durable responses
to treatment with ibrutinib monotherapy regardless of their treatment
history."

Grade 3 or 4 AEs in the pooled analysis related to ibrutinib
(investigator-assessed) decreased from 24 percent to four percent
after three years of follow-up. Grade 3 or higher serious AEs (SAEs)
related to ibrutinib also decreased over time from eight percent in
the first year to one percent after three years of treatment. No new
safety signals were observed in long-term follow-up and 64 percent of
patients remain on treatment with ibrutinib. The rate of Grade 3 or
higher adverse events or those leading to hospitalisation decreased
after one year on treatment with ibrutinib.

Combination Data

Separately, data from the Phase 1b/2 PCYC-1109 study, to be
presented today at ASCO, showed treatment with monotherapy ibrutinib
administered once-daily in combination with ofatumumab administered
intravenously is tolerated and highly active in patients with
relapsed or refractory CLL/SLL (n=71). The combination produced an 83
percent ORR in patients across all three dosing regimens studied,
including a 100 percent ORR (n=27) in patients who started with one
cycle of ibrutinib therapy followed by ofatumumab; additionally, two
patients in the study achieved a PR with lymphocytosis. Additionally,
at 12 months, the average progression-free survival (PFS) across all
patients was approximately 88 percent, with 64 percent of patients
continuing on monotherapy ibrutinib in a long-term extension study.
Three patients with Richter's transformation receiving ibrutinib and
ofatumumab achieved disease control followed by progression after Day
471, 168 and 137, respectively.

Group 2: ofatumumab Group 3: two cycles of
Group 1: one cycle on day one/cycle one ofatumumab monotherapy,
N=71 ibrutinib monotherapy, and ibrutinib on followed by ibrutinib
followed by ofatumumab day two/cycle one on day one/cycle three
(n=27) (n=20) (n=24)

ORR 100% 79% 71%
PFS at 12 months 89% 85% 90%
Median duration
of response Not reached Not reached Not reached
Best response 100% (n=23) 84% (n=19) 75% (n=24)

The most common Grade 3 or 4 AE in the study (occurring in 10
percent or more of patients) was neutropenia (17%). The most frequent
AEs (occurring in 20% or more of patients) were diarrhoea (68%),
infusion-related reaction (45%), peripheral sensory neuropathy (nerve
damage; 42%) and stomatitis (inflammation of the mouth and lips;
37%). Six patients (8%) experienced AEs leading to discontinuation of
treatment with ibrutinib. Nine patients (12.7%) died within 30 days
of the last dose and two died within the follow-up period.

CLL is a usually slow growing blood cancer that most commonly
originates from B cells, a type of white blood cell (lymphocyte) that
develops in the bone marrow. B cells are part of the immune system
and play an important role in fighting infection in the body. CLL is
the most common adult leukemia in the Western world, with the median
age at diagnosis being primarily those over 70 years old. The
incidence rates among men and women in Europe are approximately 5.87
and 4.01 cases per 100,000 persons per year, respectively. CLL is a
chronic disease; median overall survival ranges between 18 months and
more than 10 years according to the stage of disease. When cancer
cells are located mostly in the lymph nodes, the disease is called
SLL.[3-7]

About Ibrutinib

Ibrutinib is an investigational compound within a class of
medicines called Bruton's tyrosine kinase (BTK) inhibitors. BTK is an
important protein involved in mediating the cellular signalling
pathways which control B cell maturation and survival. In malignant B
cells, there is excessive signalling through the B cell receptor
signalling (BCR) pathway, which includes BTK. The malignant cell
ignores the natural signal to die and continues to develop and
proliferate. Malignant cells migrate and adhere to protective
environmental areas such as the lymph nodes where they proliferate
and survive. Ibrutinib is specifically designed to target and inhibit
BTK. Ibrutinib forms a strong covalent bond with BTK, which inhibits
the excessive transmission of cell survival signals within the
malignant B cells and stops their excessive build up in these
protected environmental areas. The efficacy and safety of ibrutinib
alone and in combination with other treatments is being studied in
several blood cancers including CLL, MCL, Waldenstrom's
macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL),
follicular lymphoma (FL) and multiple myeloma (MM).[8-12]

Ibrutinib is marketed as IMBRUVICA(R) in the U.S., where it
received approval from the U.S. Food and Drug Administration (FDA)
for the treatment of patients with MCL who have received at least one
prior therapy on November 13, 2013,[1] followed by further indication
approval for the treatment of patients with CLL who have received at
least one prior therapy on February 12, 2014.[2] The approval made
ibrutinib one of the first medications to receive FDA approval via
the Breakthrough Therapy Designation pathway (a new U.S. FDA
mechanism intended to expedite the review and development for new
medicines showing great promise to treat serious or life-threatening
conditions where there is currently an unmet medical need).

About Janssen

Janssen Pharmaceutical Companies of Johnson and Johnson are
dedicated to addressing and solving the most important unmet medical
needs of our time, including oncology (e.g. multiple myeloma and
prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g.
schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS,
hepatitis C and tuberculosis), and cardiovascular and metabolic
diseases (e.g. diabetes). Driven by our commitment to patients, we
develop sustainable, integrated healthcare solutions by working
side-by-side with healthcare stakeholders, based on partnerships of
trust and transparency. More information can be found on
http://www.janssen-emea.com/ [http://www.janssen-emea.com ]. Follow
us on http://www.twitter.com/janssenEMEA for our latest news.

Janssen in Oncology

In oncology, our goal is to fundamentally alter the way cancer is
understood, diagnosed and managed, reinforcing our commitment to the
patients who inspire us. In looking to find innovative ways to
address the cancer challenge, our primary efforts focus on several
treatment and prevention solutions. These include a focus on
hematologic malignancies, prostate cancer and lung cancer; cancer
interception with the goal of developing products that interrupt the
carcinogenic process; biomarkers that may help guide targeted,
individualized use of our therapies; as well as safe and effective
identification and treatment of early changes in the tumour
microenvironment.

(This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development. The reader is cautioned not to rely on
these forward-looking statements. These statements are based on
current expectations of future events. If underlying assumptions
prove inaccurate or unknown risks or uncertainties materialize,
actual results could vary materially from the expectations and
projections of Janssen Research & Development, LLC, any of the other
Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and
uncertainties include, but are not limited to: challenges inherent in
new product development, including obtaining regulatory approvals;
competition, including technological advances, new products and
patents attained by competitors; challenges to patents; changes in
behavior and spending patterns or financial distress of purchasers of
health care products and services; changes to governmental laws and
regulations and domestic and foreign health care reforms; general
industry conditions including trends toward health care cost
containment; and increased scrutiny of the health care industry by
government agencies. A further list and description of these risks,
uncertainties and other factors can be found in Johnson & Johnson's
Annual Report on Form 10-K for the fiscal year ended December 29,
2013, including in Exhibit 99 thereto, and our subsequent filings
with the Securities and Exchange Commission. Copies of these filings
are available online at http://www.sec.gov, http://www.jnj.com or on
request from Johnson & Johnson. None of the Janssen Pharmaceutical
companies or Johnson & Johnson undertakes to update any
forward-looking statement as a result of new information or future
events or developments.)

References

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. Accessed March 14, 2013.
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