Janssen-Cilag International NV (Janssen) Submits European Marketing Authorisation Application for Investigational Multi-Drug Resistant Tuberculosis Treatment Bedaquiline

Beerse, Belgium (ots/PRNewswire) -

Janssen-Cilag International NV (Janssen) today announced it has
submitted a Marketing Authorisation Application to the European
Medicines Agency (EMA) seeking conditional approval for the use of
the investigational drug bedaquiline (TMC207) as an oral treatment,
to be used as part of combination therapy for pulmonary, multi-drug
resistant tuberculosis (MDR-TB) in adults. If approved, bedaquiline
(Ba-DA-qui-lin) could be one of the first drugs with a new mechanism
of action for tuberculosis (TB) in more than 40 years and one of the
first ever to be specifically indicated for MDR-TB.

"MDR-TB is a growing threat to public health and it presents a
significant new treatment challenge in controlling this serious and
deadly disease," said Wim Parys, M.D., Head of the Infectious
Diseases therapeutic area at Janssen. "This filing underscores our
commitment to discover and develop novel medicines and solutions for
serious unmet medical needs, and we hope this new treatment will
become an important option for patients with MDR-TB."

The discovery of bedaquiline (formerly R207910) and its unique
mechanism of action were announced in a Science article by scientists
at Janssen. The antibiotic kills the bacterium that causes
tuberculosis (Mycobacterium tuberculosis, M.tb) by targeting
adenosine triphosphate (ATP) synthase[1], an enzyme that is essential
to generate its energy.

The regulatory submission is supported by 24-week data from the
Phase II clinical development program, which includes an open-label
study and a controlled, randomised trial that evaluated the safety
and efficacy of bedaquiline versus placebo in the treatment of
patients with pulmonary MDR-TB in combination with a background
regimen.

Among infectious diseases, TB is the second most common cause of
adult deaths worldwide and kills approximately 1.4 million people per
year[2].The World Health Organization (WHO) estimates approximately
one-third of the world's population is infected with M.tb[2]. MDR-TB
is characterised by resistance to at least two of the most powerful
medicines in today's standard, four-drug regimen for drug-susceptible
TB. In 2010, there was an estimated prevalence of 650,000 cases of
MDR-TB, and in 2008 it was estimated there were 150,000 MDR-TB deaths
annually[3]. Although the European region comprises a relatively
small percentage of global TB cases, the European region as defined
by the World Health Organisation (WHO) accounts for a large
percentage of the burden of MDR-TB[4].

Janssen also submitted a New Drug Application (NDA) to the U.S.
Food and Drug Administration (FDA) in the United States for
bedaquiline in June 2012, under priority review status.

About the clinical development program

The clinical development program includes two Phase II studies in
patients with MDR-TB. TMC207-C208 was conducted in two independent
stages: stage 1 was a controlled, randomized, exploratory trial and
stage 2 was a controlled, randomised superiority trial in MDR-TB
patients. Stage 2 compared time to culture conversion following the
use of bedaquiline (400 mg once daily for two weeks followed by 200
mg three times a week for 22 weeks) versus placebo in combination
with a standardised background regimen for MDR-TB. The study enrolled
161 patients who received treatment for 24 weeks followed by
continuation of the background therapy for an additional 12 to18
months. Results were presented in 2010 at the 41st Union World
Conference on Lung Health in Berlin, Germany[5]. Results from stage 1
were published in The New England Journal of Medicine in 2009[6]. The
submission contains 72 week data from TMC207-C208.

The submission is further supported by 24-week data from
TMC207-C209, a Phase II open-label trial in MDR-TB patients, in which
bedaquiline was administered as 400 mg once daily for two weeks
followed by 200 mg three times weekly for 22 weeks in combination
with an individualised background regimen for MDR-TB, followed by
continued administration of the background regimen for 12 to18
months. A total of 233 patients from 11 countries were enrolled in
the trial, designed to evaluate the safety and efficacy of
bedaquiline in treatment-experienced patients, including 25% with
pre-extensively drug-resistant TB (pre-XDR) and 21% with XDR-TB.
Results were presented in 2011 at the 42nd Union World Conference on
Lung Health in Lille, France[7].

The Phase III trial - TMC207-C210 - a double-blind study
comparing an intensive nine-month background regimen containing
TMC207 versus an intensive nine-month background regimen containing
placebo is planned to start recruiting in Q4 2012. This study will
evaluate a new regimen of seven drugs for a shorter treatment
duration (nine months of treatment) than the current 18 to 24 months
WHO standard of care.

About Janssen

The Janssen Pharmaceutical Companies are dedicated to addressing
and solving the most important unmet medical needs of our time,
including oncology, immunology, neuroscience, infectious diseases,
and cardiovascular and metabolic diseases. More information can be
found on http://www.janssen-emea.com.

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. For more information about Janssen
Research & Development, LLC visit http://www.janssenrnd.com.

Janssen Research & Development is part of the Janssen
Pharmaceutical Companies of Johnson & Johnson. 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.

Forward looking statements:

(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-Cilag International NV
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 financial
distress of purchasers of health care products and services; changes
to governmental laws and regulations and domestic and foreign health
care reforms; 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 Exhibit 99 of Johnson
& Johnson's Annual Report on Form 10-K for the fiscal year ended
January 1, 2012. Copies of this Form 10-K, as well as subsequent
filings, are available online at http://www.sec.gov,
http://www.jnj.com or on request from Johnson & Johnson. Neither
Janssen-Cilag International NV nor Johnson & Johnson undertake to
update any forward-looking statements as a result of new information
or future events or developments.)

References

1. Andries et al. A Diarylquinoline Drug Active on the ATP
Synthase of Mycobacterium tuberculosis Science 14 January 2005: Vol.
307. no. 5707, pp. 223 - 227.

2. World Health Organization. TB Factsheet. March 2012. Available
at: http://www.who.int/mediacentre/factsheets/fs104/en/index.html.
Accessed 16 August 2012.

3. World Health Organization, "Global TB Fact Sheet," 2011-2012.
Available at:
http://www.who.int/tb/publications/2011/factsheet_tb_2011.pdf.
Accessed 16 August 2012.

4. TB Europe Coalition, "TB in Europe," 2011. Available at
http://www.tbcoalition.eu/what-is-tuberculosis/tb-in-europe. Accessed
16 August 2012.

5. McNeeley DF. Diacon H, Pym A, et al. TMC-207 versus placebo
plus OBT for the treatment of MDR-TB: a prospective clinical trial.
Oral presentation at the 41st Union World Conference on Lung Health;
November 11-15, 2010; Berlin, Germany. Available at: http://uwclh.con
ference2web.com/content/all#/?search=mcneeley&sessions=35. Accessed
16 August.

6. Diacon et al. The Diarylquinoline TMC207 for
Multidrug-Resistant Tuberculosis, in The New England Journal of
Medicine, vol. 360 no. 23, June 4, 2009.

7. 42nd Union World Conference on Lung Health in Lille, France,
46. Clinical trials of new drugs and regimens for MDR- and XDR-TB,
October 30, 2011. Available at: http://www.worldlunghealth.org/confLi
lle/images/stories/PDF_Symposias/Symposium_46.pdf . Accessed on 16
August 2012.

ots Originaltext: Janssen-Cilag International NV (Janssen)
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