{{image}}Raritan, NJ (Press Release) - Janssen Research & Development, LLC (“Janssen”) announced the si­mul­ta­ne­ous sub­missions of a Biologic License Application (BLA) to the United States Food and Drug Ad­min­is­tra­tion (U.S. FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for siltuximab for the treat­ment of patients with multicentric Castleman disease (MCD) who are HIV-negative and human herpes virus-8 (HHV-8)-negative.

MCD is a rare disorder in which lym­pho­cytes, a certain type of white blood cells, are over-produced and lead to enlargement of lymph nodes.[1,2] This can cause a variety of symp­toms and weaken the immune system, making it hard to fight in­fec­tion. Infections in people with MCD can be very serious and may even be fatal.[3] Currently, there are no approved treat­ments in the U.S. or European Union (EU) for this rare blood disorder.

“We’re proud of our work on siltuximab. As a rare disease with a small patient pop­u­la­tion, MCD is an area of sig­nif­i­cant unmet need,” said Peter F. Lebowitz, M.D., Ph.D., global on­col­ogy thera­peutic area head, Janssen. “Siltuximab works by targeting interleukin-6 which appears to be the critical driver of this disease. By focusing on core biologic mech­a­nisms, we now have the poten­tial of helping patients with a con­di­tion that is chal­leng­ing to treat.”

Siltuximab has been granted orphan drug status in MCD in the U.S. and EU. The siltuximab regu­la­tory sub­mis­sions in­clude data from a ran­dom­ized, multi-national, double-blind, placebo-controlled study (MCD2001) and data from two non-randomized sup­port­ive studies. The MCD2001 study assessed the efficacy and safety of siltuximab plus best sup­port­ive care (BSC) compared with placebo plus BSC in patients with MCD.[4] In the study, 79 patients were ran­domly assigned in a 2:1 ratio to one of the two treat­ment groups, with 53 receiving siltuximab and BSC, and 26 receiving placebo and BSC.[5] Results of the pri­mary study analysis have been submitted for presentation at a medical meeting later this year.

About Multicentric Castleman Disease
Unlike “unicentric” Castleman disease, which is localized and affects only a single area or group of lymph nodes,[6] patients with MCD have more than one group of lymph nodes in dif­fer­en­t anatomical areas that are affected.[3] Unicentric disease can be treated by surgically removing the diseased lymph node,[7] while mul­ti­centric disease is usually much more dif­fi­cult to treat.[8] Currently, the focus of care is to reduce lymph node masses[9]^, [10] and to attempt to put the disease in remission through a com­bi­na­tion of treat­ments, in­­clud­ing corticosteroids, chemo­ther­apy and immuno­therapy. While such treat­ments may initially help, the disease often returns.[8]

MCD can also affect lymphoid tissue of internal organs, causing the liver, spleen, or other organs to enlarge.[11] Some symp­toms can be life threatening.[9,10] The most common symp­toms in­clude fever, weakness, fatigue, night sweats, weight loss, loss of appetite, nausea, vomiting and nerve damage that leads to numb­ness and weakness.[3] Infections, renal failure, and malig­nan­cies in­­clud­ing malignant lym­phoma and Kaposi’s sarcoma are common causes of death in patients with MCD.[9,10] Castleman disease is formally diag­nosed through a biopsy.[11] The number of people diag­nosed with Castleman disease is unknown, but the disease is known to be rare.[12]

About Siltuximab
Siltuximab is an inves­ti­ga­tional, anti Interleukin-6 (IL-6) chi­meric mono­clonal anti­body that targets and binds to human IL-6. IL-6 is a multifunctional cytokine produced by various cells such as T cells, B cells, mono­cytes, fibroblasts and endothelial cells.[6] Dysregulated, or imbalanced, overproduction of IL-6 from activated B cells in affected lymph nodes has been implicated in the pathogenesis of MCD.[6] Information about on­going studies with siltuximab can be found on clin­i­caltrials.gov.

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.

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 disease area strongholds that focus on hema­to­logic malig­nan­cies and prostate 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. While we continually strive to find new real-life solu­tions for cancer patients, the Janssen Pharma­ceu­tical Com­panies can provide a broad offering throughout the can­cer journey — from prevention, diag­nosis, and treat­ment — to the return to wellness.

Janssen Research & Development is part of the Janssen Pharma­ceu­tical Com­panies. Please visit http://www.janssenrnd.com for more in­­for­ma­tion.

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(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 Research & Development, LLC, any of the other Janssen Pharma­ceu­tical Com­panies 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 December 30, 2012. Copies of this Form 10-K, as well as sub­se­quent filings, are avail­able online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharma­ceu­tical Com­panies nor Johnson & Johnson under­take to update any forward-looking state­ments as a result of new in­­for­ma­tion or future events or devel­op­ments.)

References:

[1]American Cancer Society. What is Castleman disease? Available from: http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-what-is-castleman-disease. Accessed August 2013
[2] Memorial Sloan Kettering Cancer Center. Uncommon Lymphoproliferative Disorders. Available from: http://www.mskcc.org/cancer-care/adult/rare-hematologic-disorders/uncommon-lymphoproliferative-disorders. Accessed August 2013.
[3] National Center for Advancing Translational Sciences. Multicentric Castleman’s Disease. Available from: http://rarediseases.info.nih.gov/gard/9644/idiopathic-multicentric-castlemans-disease/resources/1 Accessed August 2013.
[4] A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease: Available from: http://clinicaltrials.gov/ct2/show/NCT01024036?term=MCD2001&rank=1. Accessed August 2013
[5] Internal data on file
[6] El-Osta HE, Kurzrock R. Castleman's disease: from basic mech­a­nisms to molecular thera­peutics. Oncologist. 2011;16(4):497-511.
[7] American Cancer Society. Treatment of localized (unicentric) Castleman disease. Available from: http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-treating-treating-localized. Accessed August 2013
[8] American Cancer Society. Treatment of multicentric Castleman disease. Available from: http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-treating-treating-multicentric. Accessed August 2013
[9] Peterson, B. Seminars in Oncology. Multicentric Castleman's disease. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8296200 Accessed August 2013
[10] Greiner, T. Hematology Am Soc Hematol Educ Program. Atypical Lymphoproliferative Diseases. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11701539 Accessed August 2013
[11] American Cancer Society. How is Castleman disease diag­nosed? Available from: http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-diagnosis Accessed August 2013
[12] American Cancer Society.What are the key statistics about Castleman disease? Available from: http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-key-statistics . Accessed August 2013

Source: Johnson & Johnson.