Supplemental New Drug Application for IMBRUVICA™ (ibrutinib) Submitted to the U.S. FDA

Supplemental New Drug Application for IMBRUVICA™ (ibrutinib) Submitted to the
                                   U.S. FDA

New submission based on positive Phase 3 data from the RESONATE™ trial

PR Newswire

RARITAN, N.J., April 8, 2014

RARITAN, N.J., April 8, 2014 /PRNewswire/ --Janssen Research & Development,
LLC ("Janssen") today announced the submission of a supplemental New Drug
Application (sNDA) for IMBRUVICA™ (ibrutinib) to the U.S. Food and Drug
Administration (FDA) by its collaboration partner Pharmacyclics, Inc. This
regulatory submission is based on data from the Phase 3 RESONATE™ study in
relapsed or refractory chronic lymphocytic leukemia (CLL). IMBRUVICA is being
jointly developed and commercialized by Janssen and Pharmacyclics.

In February 2014, IMBRUVICA received FDA approval to treat patients with CLL
who have received at least one prior therapy. This indication is based on an
overall response rate (ORR) from Phase 2 data and an improvement in survival
or disease-related symptoms has not been established. The current approval was
granted under the FDA's Accelerated Approval regulations and required the
completion of an additional, larger Phase 3 trial to verify clinical benefit.

The Phase 3 PCYC-1112 (RESONATE) study is a randomized, multi-center,
open-label study, which compares once-daily oral IMBRUVICA versus intravenous
ofatumumab in 391 patients with CLL or small lymphocytic lymphoma (SLL), who
had received at least one prior therapy. The RESONATE trial was halted early
in January 2014 based on the recommendation of an Independent Data Monitoring
Committee (IDMC) at the formal pre-planned interim analysis, which found
IMBRUVICA was associated with a significant improvement in progression-free
survival (the primary endpoint of the study) versus ofatumumab, and in overall
survival (a key secondary endpoint of the trial). Data from this study were
accepted and will be presented at the upcoming 50^th annual meeting of the
American Society of Clinical Oncology.

"This sNDA is the first Phase 3 submission for IMBRUVICA in the U.S. and
represents a growing and more mature body of clinical evidence to support the
use of IMBRUVICA in patients with chronic lymphocytic leukemia who have
received prior therapy," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology
Head, Janssen. "We and our collaboration partner Pharmacyclics are focused on
ways to bring this medicine to patients as quickly as possible and this is one
more important milestone in the development of this product."

CLL is a slow-growing blood cancer of white blood cells called lymphocytes,
most commonly B cells.^[1] CLL is the most common adult leukemia in the
Western world and predominantly a disease of the elderly with a median age of
diagnosis of 72.^[2] This orphan disease often eventually progresses; patients
are faced with fewer treatment options and are often prescribed multiple lines
of therapy as they relapse or become resistant to treatments.^[3]

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent of patients with mantle cell lymphoma (MCL) and 6%
of patients with CLL had Grade 3 or higher bleeding events (subdural hematoma,
ecchymoses, gastrointestinal bleeding, and hematuria). Overall, bleeding
events including bruising of any grade occurred in 48% of patients with MCL
treated with 560 mg daily and 63% of patients with CLL treated at 420 mg
daily.

The mechanism for the bleeding events is not well understood. IMBRUVICA™ may
increase the risk of hemorrhage in patients receiving antiplatelet or
anticoagulant therapies. Consider 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 with IMBRUVICA™
therapy. At least 25% of patients with MCL and 35% of patients with CLL had
infections Grade 3 or greater 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 with MCL and 35% of patients with CLL. These included
neutropenia (29%), thrombocytopenia (17%) and anemia (9%) in patients with MCL
and neutropenia (27%) and thrombocytopenia (10%) in patients with CLL. Monitor
complete blood counts monthly.

Renal Toxicity – Fatal and serious cases of renal failure have occurred with
IMBRUVICA™ therapy. Treatment-emergent increases in creatinine levels up to
1.5 times the upper limit of normal occurred in 67% of patients with MCL and
23% of patients with CLL. Increases in creatinine 1.5 to 3 times the upper
limit of normal occurred in 9% of patients with MCL and 4% of patients with
CLL. Periodically monitor creatinine levels. Maintain hydration.

Second Primary Malignancies – Other malignancies have occurred in 5% of
patients with MCL and 10% of patients with CLL who have been treated with
IMBRUVICA™. Four percent of patients with MCL had skin cancers, and 1% had
other carcinomas. Eight percent of patients with CLL had skin cancers and 2%
had other carcinomas.

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.

ADVERSE REACTIONS
CLL: The most commonly occurring adverse reactions (> 20%) in the clinical
trial were thrombocytopenia*, diarrhea (63%), bruising (54%), neutropenia*,
anemia*, upper respiratory tract infection (48%), fatigue (31%),
musculoskeletal pain (27%), rash (27%), pyrexia (25%), constipation (23%),
peripheral edema (23%), arthralgia (23%), nausea (21%), stomatitis (21%),
sinusitis (21%), and dizziness (21%).

*Treatment-emergent decreases (all grades) of platelets (71%), neutrophils
(54%) and hemoglobin (44%) were based on laboratory measurements per IWCLL
criteria and adverse reactions.

The most common Grade 3 or 4 non-hematological adverse reactions (> 5%) were
pneumonia (8%), hypertension (8%), atrial fibrillation (6.3%), sinusitis (6%),
skin infection (6%), dehydration (6.4%), and musculoskeletal pain (6%).
Treatment-emergent Grade 3 or 4 cytopenias were reported in 35% of patients.

Five patients (10%) discontinued treatment due to adverse reactions in the
trial (N=48). These included 3 patients (6%) with infections and 2 patients
(4%) with subdural hematomas. Adverse reactions leading to dose reduction
occurred in 13% of patients.

MCL: 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 (21%).

*Treatment-emergent decreases (all grades) of platelets (57%), neutrophils
(47%) and hemoglobin (41%) were based on laboratory measurements and adverse
reactions.

The most common Grade 3 or 4 non-hematological adverse reactions (> 5%) were
pneumonia (7%), abdominal pain (5%), atrial fibrillation (5.4%), 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.

DRUG INTERACTIONS
CYP3A Inhibitors – Avoid concomitant administration with strong or moderate
inhibitors of CYP3A. If a moderate CYP3A inhibitor must be used, reduce the
IMBRUVICA™ dose.
CYP3A Inducers – Avoid co-administration with strong CYP3A inducers.
SPECIAL POPULATIONS – Hepatic Impairment – Avoid use in patients with baseline
hepatic impairment.

For the full prescribing information, visit http://www.IMBRUVICA.com/.

About IMBRUVICA
IMBRUVICA was one of the first therapies to receive U.S. approval via the
FDA's Breakthrough Therapy Designation and was approved under the FDA's
Subpart H regulation.^[4] IMBRUVICA is indicated for the treatment of patients
with chronic lymphocytic leukemia (CLL) who have received at least one prior
therapy and the treatment of patients with mantle cell lymphoma (MCL) who have
received at least one prior therapy.^[5] These indications are both based on
an overall response rate (ORR). An improvement in survival or disease-related
symptoms has not been established.^[5]

IMBRUVICA works by blocking a specific protein called Bruton's tyrosine kinase
(BTK).^[5] The BTK protein transmits important signals that tell B cells to
mature and produce antibodies and is needed by specific cancer cells to
multiply and spread.^[5],[6] IMBRUVICA targets and blocks BTK, inhibiting
cancer cell survival and spread.^[5]

Janssen Biotech and Pharmacyclics are striving to make the process of
obtaining IMBRUVICA and navigating insurance benefits easy for patients. The
YOU&i Access™ program is designed specifically for patients who are prescribed
IMBRUVICA and provides personalized attention coupled with access services
designed to make obtaining medication simple and convenient for patients and
those involved in their care.

This includes a YOU&i Access™ Instant Savings program, which provides co-pay
support and benefits information to eligible commercially-insured patients.
Patients can access the program by contacting 1-877-877-3536, option 1 or by
visiting www.IMBRUVICA.com.

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 is part of the Janssen
Pharmaceutical Companies. Please visit www.janssenrnd.comfor more
information.

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 tumor 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 and/or Johnson & Johnson. Risks and
uncertainties include, but are not limited to: economic factors, such as
interest rate and currency exchange rate fluctuations; competition, including
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
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 www.sec.gov, www.jnj.com or on
request from Johnson & Johnson. Neither Janssen nor Johnson & Johnson
undertakes to update any forward-looking statement as a result of new
information or future events or developments.)

[1] American Cancer Society. Detailed guide: what is chronic lymphocytic
leukemia. Available from:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf
Accessed March 2014.
[2] Decision Resources estimate 2013.
[3] Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic
lymphocytic leukemia. Cancer Control. 2012 Jan;19(1):37-53.
[4] The U.S. Food and Drug Administration. CFR - Code of Federal Regulations
Title 21. Available from:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=314&showFR=1&subpartNode=21:5.0.1.1.4.8.
Accessed March 2014.
[5] IMBRUVICA Prescribing Information, February 2014.
[6] Genetics Home Reference. Isolated growth hormone deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed March 2014.

Media Inquiries:
Lisa Vaga
Phone: 1-908-218-7316
Mobile: 1-908-670-0363

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

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

Louise Mehrotra
Phone: 1-732-524-6491

Medical Information:
Pharmacyclics Medical Information:
1-877-877-3536

SOURCE Janssen Research & Development, LLC

Website: http://www.janssenrnd.com
 
Press spacebar to pause and continue. Press esc to stop.