Janssen Submits Additional Marketing Applications for ZYTIGA® in the European Union and in the U.S.

Beerse, Belgium And Raritan, New Jersey (ots/PRNewswire) -

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Simultaneous Submissions Based on Data from Pre-chemo
Prostate Cancer Study

Janssen-Cilag International NV announced today it has submitted a
type II variation to the European Medicines Agency (EMA) for
ZYTIGA(R); simultaneously, Janssen Research & Development, LLC
submitted a supplemental New Drug Application (sNDA) to the U.S. Food
and Drug Administration (FDA); Both applications are intended to
extend the use of ZYTIGA administered with prednisone for the
treatment of patients with metastatic castration resistant prostate
cancer (mCRPC) who are asymptomatic or mildly symptomatic after
failure of androgen deprivation therapy and before chemotherapy.

Both regulatory applications follow the announcement [http://www
.prnewswire.co.uk/news-releases/zytiga-plus-prednisone-show-improveme
nts-in-asymptomatic-or-mildly-symptomatic-chemotherapy-naive-patients
-with-metastatic-castration-resistant-prostate-cancer-156570325.html
] of results observed from pre-specified interim analyses of the
international Phase 3, randomized, double-blind, placebo-controlled
COU-AA-302 clinical study. This study, which included 1,088
asymptomatic or mildly symptomatic men with mCRPC who had not
received chemotherapy, evaluated the effect of ZYTIGA plus prednisone
on the co-primary endpoints of radiographic progression-free survival
(rPFS) and overall survival (OS) compared to placebo plus prednisone.
Data from this study were presented at the 48th Annual Meeting of the
American Society of Clinical Oncology (ASCO) earlier this month.

"We're delighted to move forward so quickly with these regulatory
submissions, building on the momentum created by the data
presentation two weeks ago," said Michael L. Meyers, M.D., Ph.D.,
Vice President, Compound Development Team Leader, ZYTIGA. "We look
forward to working with the FDA and EMA to make ZYTIGA available for
men with metastatic prostate cancer earlier in the course of their
disease."

The company previously announced the study was unblinded based on
the unanimous recommendation of an Independent Data Monitoring
Committee (IDMC). Based on these results, the IDMC also recommended
that patients in the control arm be offered treatment with ZYTIGA.

"As a company, we strive to develop innovative therapeutic
options that meet the unmet needs of patients suffering from
devastating diseases such as mCRPC," said William N. Hait, M.D.,
Ph.D., Global Head, Janssen Research & Development and Head, Oncology
Therapeutic Area. "These regulatory submissions for ZYTIGA are a
clear example of our efforts to bring extraordinary oncologic
therapies to those with the greatest need."

About ZYTIGA

ZYTIGA in combination with prednisone was approved by the U.S.
Food and Drug Administration (FDA) in April 2011 and by the European
Commission in September 2011 for the treatment of men with mCRPC who
have received prior chemotherapy containing docetaxel.

About Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson are
dedicated to addressing and solving the most important unmet medical
needs of our time, including oncology, immunology, neuroscience,
infectious disease, and cardiovascular and metabolic diseases. Driven
by our commitment to patients, we work together to bring innovative
ideas, products, services and solutions to address serious unmet
medical needs around the world. More information can be found at
http://www.janssen-emea.com

About Janssen Research & Development, LLC

Janssen Research & Development, LLC is headquartered in Raritan,
N.J. and has affiliated facilities in Europe, the United States and
Asia. Janssen Research & Development is leveraging a combination of
internal and external innovation to discover and develop novel
medicines and solutions in five distinct therapeutic areas:
Neuroscience, Oncology, Immunology, Infectious Diseases and Vaccines,
and Cardiovascular and Metabolism.

Important Safety Information

Contraindications - ZYTIGA(R) (abiraterone acetate) is not for
use in women. Abiraterone acetate is contraindicated in women who are
or may potentially be pregnant.

Hypertension, Hypokalemia and Fluid Retention Due to
Mineralocorticoid Excess - Use with caution in patients with a
history of cardiovascular disease or with medical conditions that
might be compromised by increases in hypertension, hypokalemia, and
fluid retention. ZYTIGA(R) may cause hypertension, hypokalemia, and
fluid retention as a consequence of increased mineralocorticoid
levels resulting from CYP17 inhibition. Safety has not been
established in patients with LVEF <50% or New York Heart Association
(NYHA) Class III or IV heart failure because these patients were
excluded from the randomised clinical trial. Control hypertension and
correct hypokalemia before and during treatment.

Monitor blood pressure, serum potassium, and symptoms of fluid
retention before treatment and at least monthly thereafter.

Adrenocortical Insufficiency (AI) - AI has been reported in
clinical trials in patients receiving ZYTIGA(R) in combination with
prednisone, after an interruption of daily steroids and/or with
concurrent infection or stress. Use caution and monitor for symptoms
and signs of AI if prednisone is stopped or withdrawn, if prednisone
dose is reduced, or if the patient experiences unusual stress.
Symptoms and signs of AI may be masked by adverse reactions
associated with mineralocorticoid excess seen in patients treated
with ZYTIGA(R). Perform appropriate tests, if indicated, to confirm
AI. Increased dosages of corticosteroids may be used before, during,
and after stressful situations.

Hepatotoxicity - Increases in liver enzymes have led to
interruption, dose modification, and/or discontinuation of ZYTIGA(R).
Monitor liver function and modify, withhold, or discontinue ZYTIGA(R)
dosing as recommended (see Prescribing Information for further
details). Measure serum transaminases prior to starting treatment
with ZYTIGA(R), every two weeks for the first three months of
treatment, and monthly thereafter. If clinical symptoms or signs
suggestive of hepatotoxicity develop, serum transaminases, in
particular serum ALT, should be measured immediately. If at any time
the ALT rises above 5 times the upper limit of normal, treatment
should be interrupted immediately and liver function closely
monitored. Re-treatment may take place only after return of liver
function tests to the patient's baseline and at a reduced dose level.
If patients develop severe hepatotoxicity (ALT 20 times the upper
limit of normal) anytime while on therapy, treatment should be
discontinued and patients should not be re-treated.

The safety of ZYTIGA(R) in patients with baseline severe hepatic
impairment has not been studied. These patients should not receive
ZYTIGA(R).

Food Effect - ZYTIGA(R) must be taken on an empty stomach.
Exposure to abiraterone increases up to 10-fold when ZYTIGA(R) is
taken with meals. No food should be eaten for at least two hours
before the dose of ZYTIGA(R) is taken and for at least one hour after
the dose of ZYTIGA(R) is taken. Abiraterone Cmax and
AUC0-lemniscate(exposure) were increased up to 17- and 10-fold,
respectively, when a single dose of ZYTIGA(R) was administered with a
meal compared to a fasted state.

Adverse Reactions - The most common adverse reactions (greater
than or equal to 1/10) are hypokalemia, peripheral oedema, urinary
tract infection and hypertension.

Drug Interactions - ZYTIGA(R) is an inhibitor of the hepatic
drug-metabolising enzyme CYP2D6. Caution is advised when ZYTIGA(R) is
administered with medicinal products activated by or metabolised by
CYP2D6, particularly with medicinal products that have a narrow
therapeutic index. Dose reduction of medicinal products with a narrow
therapeutic index that are metabolised by CYP2D6 should be
considered. Examples of medicinal products metabolised by CYP2D6
include metoprolol, propranolol, desipramine, venlafaxine,
haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone
and tramadol (the latter three products requiring CYP2D6 to form
their active analgesic metabolites).

Based on in vitro data, ZYTIGA(R) is a substrate of CYP3A4. The
use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin,
ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g.,
phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine,
phenobarbital) should be avoided, or used with caution during
treatment with ZYTIGA(R).

ots Originaltext: Janssen Pharmaceutica
Im Internet recherchierbar: http://www.presseportal.de

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office,
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+1-908-218-7316
office, +1-908-670-0363 cell. .Investor Relations: Stan Panasewicz,
+1-732-524-2524 office. Louise Mehrotra, +1-732-524-6491 office