Janssen-Cilag International NV (Janssen)

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.)


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.


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