Ibrutinib Phase 2 Data: Analyses Show Efficacy with Ibrutinib Monotherapy in Patients with Relapsed or Refractory Mantle Cell or

 Ibrutinib Phase 2 Data: Analyses Show Efficacy with Ibrutinib Monotherapy in
   Patients with Relapsed or Refractory Mantle Cell or Diffuse Large B-cell
                                   Lymphoma

Data presented at the European Hematology Association (EHA) Annual Congress

PR Newswire

RARITAN, N.J., June 16, 2013

RARITAN, N.J., June 16, 2013 /PRNewswire/ --Janssen Research & Development,
LLC (Janssen), today announced the results of two separate Phase 2 studies
suggesting that ibrutinib, an investigational oral Bruton's tyrosine kinase
(BTK) inhibitor, shows efficacy when used as a monotherapy in patients with
relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell
lymphoma (DLBCL). The studies were presented today at the European Hematology
Association (EHA) 18^th Annual Congress in Stockholm, Sweden. Ibrutinib is
being jointly developed by Janssen and Pharmacyclics, Inc.

"Our comprehensive clinical development program is studying ibrutinib across a
variety of B-cell malignancies; these patients, including those with DLBCL and
MCL, are in real need of new treatment options," said Peter F. Lebowitz, M.D.,
Ph.D., Global Oncology Therapeutic Area Head, Janssen R&D. "It's particularly
exciting to observe the differences in response rates now as compared to
earlier data from this study that were presented several months ago."

Ibrutinib in Relapsed/Refractory MCL
In relapsed/refractory MCL patients treated with ibrutinib monotherapy the key
results include:

  oAn overall response rate (ORR) of 68%, including a complete response (CR)
    of 21% and a partial response (PR) of 47%.
  oThe estimated median duration of response (DOR) in all responding patients
    was 17.5 months. Median progression-free survival (PFS) was 13.9 months.
    Median overall survival (OS) has not yet been reached, but is estimated to
    be 58% at 18 months.
  oTreatment-emergent adverse events (AEs) were seen in greater than 20% of
    patients and included diarrhea (50%), fatigue (41%), nausea (31%),
    peripheral edema (28%), dyspnea (27%), constipation (25%), upper
    respiratory tract infection (23%), vomiting (23%) and decreased appetite
    (21%) and were consistent with previously reported data. Only 7% of
    patients discontinued due to an AE.

"The results of this single-agent study are encouraging. It is exciting to see
how active ibrutinib is in the treatment of relapsed and refractory mantle
cell lymphoma, particularly as the responses appear to last.," said Professor
Simon Rule, Consultant Haematologist in the Department of Haematology at the
Derriford Hospital in Plymouth, United Kingdom. "What is equally important is
that no new safety signals were observed during this study."

The MCL study was a Phase 2 multicenter, open-label, study including 111
patients with relapsed/refractory MCL at 18 sites internationally. Patients
had received a median of three prior therapies and were enrolled into two
cohorts based on prior bortezomib exposure – either bortezomib-naive (n=63) or
bortezomib-exposed (n=48), with both groups receiving 560 mg of ibrutinib
orally, once a day. The primary endpoint of the study was ORR. Secondary
endpoints included DOR, PFS, OS and frequency and severity of adverse events.

Ibrutinib in Relapsed/Refractory DLBCL
In the second Phase 2 study involving patients with relapsed/refractory DLBCL
(n=70), investigators tested the hypothesis that ibrutinib would be more
active in the Activated B-cell-like (ABC) subtype compared to the Germinal
Center B-cell-like (GCB) subtype, given that the ABC subtype is dependent on
the B-cell antigen receptor (BCR) pathway. Ibrutinib targets the BCR pathway
by inhibiting BTK, a critical mediator in malignant B-cell growth and
proliferation. Results of the study show that:

  oPatients with the ABC subtype showed a significantly greater response to
    ibrutinib monotherapy compared to those with the GCB subtype (ORR = 41% vs
    5%, p=0.007, Fisher's exact test).
  oMedian OS was 9.76 months for the ABC subtype, compared to 3.35 months for
    the GCB subtype (p=0.05).
  oWithin the ABC subtype group, only patients who had a CD79B mutation
    responded to treatment; patients with only an MYD88 mutation did not
    respond to treatment, suggesting a MYD88-dependent but BCR-independent
    pathogenesis for some DLBCL tumors.
  oSafety data from 70 patients identified no new safety signals. Grade 3 or
    higher AEs were seen in greater than 3% of patients and included fatigue
    (9%), hyponatremia (9%), pneumonia (7%), dehydration (4%), and pleural
    effusion (4%).

"These results indicate the important function BTK plays in the survival of
ABC type DLBCL," explained presenting investigator Sven de Vos, M.D., Ph.D.,
Associate Professor in the Department of Medicine at the UCLA Medical Center,
Los Angeles, who reported the results at the EHA Congress today. "Seeing
clinically meaningful responses among the ABC subtype was encouraging, as
patients at this stage are challenging to treat. Additional trials among this
patient group are ongoing."

The DLBCL study was a Phase 2 multicenter, open-label, study that included 70
patients with relapsed/refractory DLBCL with a median of three prior
therapies. All patients underwent gene expression profiling to determine their
DLBCL subtype, 29 patients were identified with the ABC subtype, and 20
withthe GCB subtype. Patients received ibrutinib 560 mg orally, once a day,
until disease progression or unacceptable toxicity. The primary objective of
the study was to assess ORR categorized by subtype, with secondary objectives
being to assess the safety and tolerability of ibrutinib in people with DLBCL.

About Ibrutinib
Ibrutinib is an investigational, oral BTK inhibitor. The effectiveness and
safety of ibrutinib alone or in combination with other treatments is being
studied in several B-cell malignancies.

Janssen Biotech, Inc. and Pharmacyclics entered into a collaboration and
license agreement in December 2011 to co-develop and co-commercialize
ibrutinib. The regulatory filing for ibrutinib in MCL is expected to be made
prior to the end of the third quarter of 2013. Details about the complete
ibrutinib clinical program is posted on clinicaltrials.gov.

To date, ibrutinib has been granted three Breakthrough Therapy Designations by
the U.S. Food & Drug Administration (FDA) as a monotherapy for the treatment
of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL) with deletion of the short arm of chromosome 17 (del17p);
patients with relapsed/refractory MCL who have received prior therapy, and in
patients with Waldenstrom's macroglobulinemia (WM). The implications of
Breakthrough Therapy Designation cannot be determined at this time.

About B-Cell Malignancies
Both MCL and DLBCL are part of a family of blood cancers which originate from
malignant B-cells. Unlike healthy B-cells, malignant B-cells ignore signals to
die and continue to develop and reproduce in the lymph.[1][2][3]When a
malignancy is described as 'relapsed', it means that it has returned after an
initial partial or total remission.[4] 'Refractory' refers to cancer that has
become resistant to current treatment.[5]

About Janssen Research & Development, LLC
At Janssen, we are dedicated to addressing and solving some of the most
important unmet medical needs of our time in oncology, immunology,
neuroscience, infectious diseases and vaccines, and cardiovascular and
metabolic diseases. Driven by our commitment to patients, we develop
innovative products, services and healthcare solutions to help people
throughout the world. Janssen Research & Development and Janssen Biotech are
part of the Janssen Pharmaceutical Companies. Please visit
http://www.janssenrnd.com for more information.

(This press release contains "forward-looking statements" as defined in the
Private Securities Litigation Reform Act of 1995. 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 and/or Johnson & Johnson. Risks and uncertainties include,
but are not limited to, general industry conditions and competition; economic
factors, such as interest rate and currency exchange rate fluctuations;
technological advances, new products and patents attained by competitors;
challenges inherent in new product development, including obtaining regulatory
approvals; challenges to patents; changes in behavior and spending patterns or
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to governmental laws and regulations and domestic and foreign health care
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description of these risks, uncertainties and other factors can be found in
Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal
year ended December 30, 2012. Copies of this Form 10-K, as well as subsequent
filings, are available online at www.sec.gov, www.jnj.com or on request from
Johnson & Johnson. None of the Janssen Pharmaceutical Companies  nor Johnson &
Johnson undertake to update any forward-looking statements as a result of new
information or future events or developments.)

Media Inquiries:
Kellie McLaughlin
Phone: 1-908-927-7477
Mobile: 1-609-468-8356

Investor Relations:
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Phone: 1-732-524-2524

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Phone: 1-732-524-6491

U.S. Medical Information, Phamacyclics:
855-ibrutinib [(855) 427-8846]

References

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[1] Murphy K, Travers P, Walport M. Janeway's Immunobiology. 7th ed. Garland
Science; 2008:257-320.
[2] Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side
of B-cell differentiation. Nat Rev Immunol. 2002. Dec; 2(12):920-32.
[3] LeBien TW, Tedder, TF. B lymphocytes: how they develop and function.
Blood. 2008; 112(5):1570-1580.
[4] PubMed Health. Relapse Definition. Available at:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0032674/def-item/glossary_CDR0000045866/?report=objectonly.
Accessed November 19, 2012.
[5] PubMed Health. Refractory Cancer Definition. Available at:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0032674/def-item/glossary_CDR0000045863/?report=objectonly.
Accessed November 19, 2012.

SOURCE Janssen

Website: http://www.janssenrnd.com
 
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