IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One

  IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic
      Lymphocytic Leukemia Who Have Received At Least One Prior Therapy

PR Newswire

HORSHAM, Pa., Feb. 12, 2014

HORSHAM, Pa., Feb. 12, 2014 /PRNewswire/ --Janssen Biotech, Inc. ["Janssen"]
today announced the U.S. Food and Drug Administration (FDA) has approved
IMBRUVICA™ (ibrutinib) capsules for the treatment of patients with chronic
lymphocytic leukemia (CLL) who have received at least one prior therapy.^1
IMBRUVICA was first approved in November 2013 for the treatment of patients
with mantle cell lymphoma (MCL) who have received at least one prior
therapy.^1 Both indications are based on an overall response rate (ORR). An
improvement in survival or disease-related symptoms has not been
established.^1

(Photo: http://photos.prnewswire.com/prnh/20140212/NY62006 )

IMBRUVICA is the first once-daily, single-agent, oral Bruton's tyrosine kinase
(BTK)inhibitor for patients with CLL who have received one prior therapy and
is being jointly developed and commercialized by Janssen and Pharmacyclics,
Inc. Both indications were granted priority review and were approved under the
FDA's accelerated approval program; in addition, IMBRUVICA is one of the first
medicines with the FDA's Breakthrough Therapy Designation to receive U.S.
approval.

CLL is a slow-growing blood cancer of white blood cells called lymphocytes,
most commonly B cells.^2 CLL is an orphan disease (which is defined as a
disease impacting fewer than 200,000 Americans^3) and is primarily diagnosed
in those over 70 years old.^2 In the U.S., an estimated 16,000 people are
diagnosed with CLL each year^4 and it is estimated that nearly 4,600 will
unfortunately die due to this disease.^5 The U.S. prevalence of CLL is
approximately 114,500 people.^6

"CLL is a challenging disease and many physicians switch their patients from
therapy to therapy as their disease relapses.There has been a significant
need for new alternatives for these patients,"said John C. Byrd, M.D.,
director, Division of Hematology, The Ohio State University Comprehensive
Cancer Center – Arthur G. James Cancer Hospital & Richard J. Solove Research
Institute and lead investigator for pivotal CLL trial PCYC-1102-CA.^+"The
approval of IMBRUVICA provides a new, once-daily oral therapy option for
physicians."

"The speed at which we were able to bring IMBRUVICA to this point epitomizes
the sense of urgency that drives oncology drug developers to bring important
new medicines to patients in need," said Craig Tendler, M.D., vice president,
Late-Stage Development and Global Medical Affairs for Oncology,Janssen.
"We're delighted and proud of today's approval, because it represents our
commitment to making a difference for patients. We appreciate the ongoing
collaboration between the companies and the FDA, which made this possible."

IMBRUVICA works by blocking a specific protein called BTK.^1 Non-clinical
studies have shown that blocking BTK inhibits the enzyme needed by the cancer
to multiply and spread.^1

IMBRUVICA in CLL
The safety and efficacy of IMBRUVICA in patients with relapsed or refractory
CLL were evaluated in an open-label, multi-center Phase 1b/2 trial
(PCYC-1102-CA) of 48 patients for a median treatment duration of 15.6
months.^1 IMBRUVICA was administered at 420 mg once daily until disease
progression or until no longer tolerated by the patient. TheORR and duration
of response (DOR)wereevaluated according to a modified version of the
International Workshop on CLL (IWCLL) criteria by an Independent Review
Committee. ORR was 58.3 percent of patients (95% confidence interval (CI) (%),
43.2, 72.4), all partial responses. None of the patients had a complete
response.The DOR ranged from 5.6 to 24.2+ months. The median DOR was not
reached.^1

The Warnings and Precautions for IMBRUVICA include hemorrhage, infections,
myelosuppression (reduced ability for the bone marrow to produce blood cells),
renal toxicity, second primary malignancies and embryo-fetal toxicity.^1 For
more information about Warnings and Precautions, please see page four of this
release.

The most common Grade 3 or 4 non-hematological adverse reactions (occurring in
five percent or more of patients) were pneumonia (8%), hypertension (8%),
atrial fibrillation (6.3%), sinusitis (6%), skin infection (6%), dehydration
(6.4%) and musculoskeletal pain (6%). The most commonly occurring side effects
(adverse reactions in 20 percent or more of CLL patients 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 (fever, 25%), constipation
(23%), peripheral edema (23%), arthralgia (joint pain, 23%), nausea (21%),
stomatitis (inflammation in the mouth, 21%), sinusitis (21%) and dizziness
(21%).^1 (Note: *Treatment-emergent decreases (all grades) of platelets (71%),
neutrophils (54%) and hemoglobin (44%) were based on laboratory measurements
per IWCLL criteria and adverse reactions.)

Five patients (10%) discontinued treatment due to adverse reactions in the
clinical trial (N=48). These included three patients (6%) with infections and
two patients (4%) with subdural hematomas. Adverse reactions leading to dose
reduction occurred in 13 percent of patients.^1

The recommended dose of IMBRUVICA for CLL is 420 mg (three 140 mg capsules)
orally once daily.^1

The IMBRUVICA PCYC-1102-CA CLL study was published online in The New England
Journal of Medicine in June 2013.^7

Janssen and Pharmacyclics are continuing an extensive clinical development
program for IMBRUVICA, including Phase 3 study commitments in multiple patient
populations.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent of patients with 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 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.^1 These indications are both based on an overall response rate
(ORR). An improvement in survival or disease-related symptoms has not been
established.^1 IMBRUVICA was approved under the FDA's Subpart H regulation.^8
For more information, visit http://www.imbruvica.com/.

IMBRUVICA works by blocking a specific protein called Bruton's tyrosine kinase
(BTK).^1 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.^1,9 IMBRUVICA targets and blocks BTK, inhibiting cancer
cell survival and spread.^1

Janssen Biotech is 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 Biotech, Inc.
Janssen Biotech, Inc. redefines the standard of care in immunology, oncology,
urology and nephrology. Built upon a rich legacy of innovative firsts, Janssen
Biotech has delivered on the promise of new treatments and ways to improve the
health of individuals with serious disease. Beyond its innovative medicines,
Janssen Biotech is at the forefront of developing education and public policy
initiatives to ensure patients and their families, caregivers, advocates and
health care professionals have access to the latest treatment information,
support services and quality care. For more information on Janssen Biotech,
Inc. or its products, visit www.janssenbiotech.com.

Janssen Biotech is one of the Janssen Pharmaceutical Companies of Johnson &
Johnson, which are dedicated to addressing and solving some of the most
important unmet medical needs in oncology, immunology, neuroscience,
infectious diseases and vaccines, and cardiovascular and metabolic diseases.
Driven by our commitment to patients, we work together to bring innovative
ideas, products, services and solutions to people throughout the world. Follow
us on Twitter at www.twitter.com/JanssenUS.

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, including regarding plans
for further clinical development of IMBRUVICA. 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 Biotech, Inc.
or Johnson & Johnson. Risks and uncertainties include, but are not limited to,
technological advances, new products and patents attained by competitors;
challenges and difficulties inherent in new product development, including
obtaining regulatory approvals; manufacturing difficulties or delays; and
trends toward health care cost containment. A further list and description of
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 and in its subsequent reports on Form 10-Q and Form 8-K. Copies of these
filings are available online at www.sec.gov, www.jnj.com or on request from
Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson &
Johnson undertakes to update any forward-looking statements as a result of new
information or future events or developments.)

^+Disclaimer: Dr. Byrd serves as national principal investigator of this
Pharmacyclics-sponsored clinical study forming the basis for ibrutinib
FDA-approval. He has served as an unpaid advisor to both Pharmacyclics and
Janssen in developing the compound ibrutinib. Dr. Byrd does not have a
financial interest in either company.

^1 IMBRUVICA Prescribing Information, February 2014
^2 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 January 2014.
^3 National Organization for Rare Disorders. "Rare Disease Information".
Available from:
http://www.rarediseases.org/rare-disease-information/rare-disease-information.
Accessed January 2014.
^4 National Cancer Institute. What You Need To Know About™ Leukemia. Available
from http://www.cancer.gov/cancertopics/wyntk/leukemia/page4. Accessed January
2014.
^5 National Comprehensive Cancer Network. NCCN Guidelines Version 1.2014:
Non-Hodgkin's Lymphomas. Available from:
http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed January
2014.
^6IMS patient claims estimates for July 2012-June 2013. Note: This
information is an estimate derived from the use of information under license
from the following IMS Health Incorporated information service: IMS Oncology
Tracking Reports for the period July 2012 to June 2013. IMS expressly reserves
all rights, including rights of copying, distribution and republication.
Pharmacyclics, Inc. makes no representation with respect to the accuracy or
reliability of this information. Investors are advised toindependently verify
this information before using it to make investment decisions.
^7 Byrd JC et al. Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic
Leukemia. N Engl J Med 2013;369(1):32-42.
^8 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 January 2014.
^9 Genetics Home Reference. Isolated growth hormone deficiency. Available
from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed January 2014.

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SOURCE Janssen Biotech, Inc.

Website: http://www.janssenbiotech.com
 
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