SYLVANT™ (siltuximab) Receives FDA Approval to Treat Multicentric Castleman's Disease (MCD)

SYLVANT™ (siltuximab) Receives FDA Approval to Treat Multicentric Castleman's
                                Disease (MCD)

First treatment approved for patients with rare blood disorder

PR Newswire

HORSHAM, Pa., April 23, 2014

HORSHAM, Pa., April 23, 2014 /PRNewswire/ --Janssen Biotech, Inc. ["Janssen"]
today announced the U.S. Food and Drug Administration (FDA) has approved
SYLVANT™ (siltuximab) for the treatment of patients with multicentric
Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative
and human herpesvirus-8 (HHV-8) negative. SYLVANT was not studied in patients
with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind
to virally produced interleukin-6 (IL-6) in a nonclinical study. SYLVANT is an
IL-6 antagonist biologic therapy administered as an intravenous (IV) infusion
once every three weeks.^1 SYLVANT is the first approved treatment in the U.S.
for MCD.

SYLVANT 100 and 400 mg Vials

MCD is a rare blood disorder with high morbidity in which lymphocytes, a type
of white blood cell, are over-produced, leading to enlarged lymph nodes. MCD
can also affect lymphoid tissue of internal organs, causing the liver, spleen
or other organs to enlarge.^2 Infections, multisystem organ failure and
malignancies including malignant lymphoma are common causes of death in
patients with MCD.^2,3,4,5

"There has been a serious need for treatment options for patients with MCD,"
said Frits van Rhee, M.D., Ph.D., University of Arkansas for Medical Sciences,
and MCD2001 study lead investigator. "MCD is a complex disease and up until
this point, physicians have tried to reduce lymph node masses and put the
disease in remission through a combination of treatments, but MCD often
returns. ^ Today's approval of SYLVANT gives physicians a long-awaited
treatment option for a group of patients who has been suffering with this
chronic, serious and debilitating disease."

MCD is a proliferative disease that acts very much like lymphoma (cancer of
lymph nodes). It is so rare that it is difficult to track the number of
cases,^2 though a recent U.S. analysis estimates* the incidence of MCD at
approximately 1,100 to 1,300 Americans.^6

"Today's approval of a treatment for patients with multicentric Castleman's
disease marks a significant milestone for patients living with this rare
disease and underscores the importance of ongoing research and development in
areas where there are so few patients with such a high unmet medical need,"
said Peter L. Saltonstall, president and CEO, National Organization of Rare
Disorders (NORD), a federation of health organizations dedicated to helping
people with rare diseases.

While the cause of MCD currently is unknown, overproduction of IL-6 is
considered a key mechanism in MCD.^2,7 SYLVANT works by binding to human IL-6,
a multifunctional cytokine produced by various cells such as T cells, B cells,
monocytes, fibroblasts and endothelial cells.^1,7

"SYLVANT exemplifies Janssen's approach to research and development, as well
as our commitment to patients," said Peter F. Lebowitz, M.D., Ph.D., Global
Oncology Head, Janssen. "Our expertise in hematologic malignancies was key to
recognizing the potential for SYLVANT in this rare disease. We're extremely
proud to be the first company with an approved medicine to treat MCD in the

About the MCD2001 Pivotal Study
The efficacy and safety of SYLVANT were evaluated in a multi-national,
randomized, double-blind, placebo-controlled pivotal study in 79 patients with
MCD (MCD2001). MCD2001 is the first randomized study in MCD.^8 Fifty-three
patients were randomized to the SYLVANT arm at a dose of 11 mg/kg and 26
patients were randomized to the placebo arm. Patients had symptomatic MCD and
were HIV negative and HHV-8 negative.^1

Treatment of MCD tumors and related symptoms is an important treatment goal
for these patients. In this pivotal study, which led to the FDA approval, more
than one-third of patients in the SYLVANT arm had a durable tumor and
symptomatic response to treatment plus best supportive care (BSC), compared to
none of the patients who received placebo plus BSC (34 percent versus 0
percent; 95 percent CI: 11.1, 54.8; p=0.0012). A durable response was defined
as tumor and symptomatic response (reduction in tumor size and disease
symptoms) that persisted for a minimum of 18 weeks without treatment failure.
The median time to treatment failure was not reached for patients who received
SYLVANT plus BSC; those who received placebo plus BSC experienced treatment
failure at a median of 134 days (p<0.05). Efficacy results from MCD2001 also
showed tumor response for those in the SYLVANT arm was 38 percent versus four
percent for those in the placebo arm (p<0.05). Among anemic patients, an
increase in hemoglobin of 1.5 g/dL was seen in 61 percent of patients in the
SYLVANT arm versus 0 percent in patients who received placebo and BSC

The warnings and precautions for SYLVANT include concurrent active severe
infections, administration of live vaccines, infusion related reactions and
hypersensitivity and gastrointestinal perforation.^1 For more information
about warnings and precautions, please see below in this press release.

The most frequent adverse reactions (greater than 10 percent compared to
placebo) during treatment with SYLVANT in the MCD clinical trial were rash (28
percent), pruritus (itching) (28 percent), upper respiratory tract infection
(26 percent), increased weight (19 percent) and hyperuricemia (high uric acid
level) (11 percent).^1

*Estimate from a U.S. claims database

Access to SYLVANT
Janssen Biotech is committed to helping patients obtain access to our
medicines by offering comprehensive access services and support for patients.
The SylvantOne™ Support program offers a variety of services for providers and
patients that can help assess insurance coverage and identify cost support
options, such as the SylvantOne™ Patient Rebate Program for eligible
commercial patients, as well as a potential option for those who are
uninsured. Patients and providers can contact SylvantOne™ Support by calling

About SYLVANT™ (siltuximab)
SYLVANT is an anti-interleukin-6 (IL-6) chimeric monoclonal antibody that
binds to human IL-6.^1 IL-6 is a multifunctional cytokine produced by various
cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells.
Dysregulated overproduction of IL-6 from activated B cells in affected lymph
nodes has been implicated in the pathogenesis of, or mechanism causing, MCD.^7
Information about ongoing studies with siltuximab can be found at

On September 3, 2013, Janssen announced 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 MCD
who are HIV negative and HHV-8 negative. The FDA granted the siltuximab BLA
priority review in the U.S. and the EMA has granted Accelerated Assessment of
the MAA. Siltuximab has been granted orphan drug status in MCD in the U.S. and
European Union.

About multicentric Castleman's disease (MCD)
MCD is a rare blood disorder with high morbidity in which lymphocytes, a type
of white blood cell, are over-produced and lead to enlargement of lymph nodes.
MCD can also affect lymphoid tissue of internal organs, causing the liver,
spleen or other organs to enlarge.^2 Signs and symptoms are driven by
dysregulated IL-6 production.^2,7 Common symptoms include enlarged lymph nodes
(appearing as lumps under the skin), fever, weakness, fatigue, night sweats,
weight loss, loss of appetite, nausea, vomiting and nerve damage that leads to
numbness and weakness.^2 Some symptoms can be life threatening.  Infections,
multisystem organ failure and malignancies including malignant lymphoma are
common causes of death in patients with MCD.^2,3,4,5 ^

Unlike "unicentric" Castleman's disease, which is localized and affects only a
single area or group of lymph nodes, ^ patients with MCD have more than one
group of lymph nodes in different anatomical areas that are affected.
Unicentric disease can be treated by surgically removing the diseased lymph
node, while multicentric disease is usually much more difficult to treat.^2,7

Castleman's disease is formally diagnosed through a lymph node biopsy. The
number of people diagnosed with Castleman's disease is unknown, but the
disease is known to be rare.^2


CONTRAINDICATIONS - Severe hypersensitivity reaction to siltuximab or any of
the excipients in SYLVANT.

Concurrent Active Severe Infections - Do not administer to patients with
severe infections until the infection resolves. Monitor patients closely for
infections. Institute prompt anti-infective therapy and do not administer
further SYLVANT until the infection resolves.

Vaccinations - Do not administer live vaccines to patients receiving SYLVANT
because interleukin-6 (IL-6) inhibition may interfere with the normal immune
response to new antigens.

Infusion Related Reactions and Hypersensitivity - Stop the infusion if the
patient develops signs of anaphylaxis. Discontinue further therapy.

Stop the infusion if the patient develops mild to moderate infusion reactions.
If the reaction resolves, the infusion may be restarted at a lower infusion
rate. Consider medicating with antihistamines, acetaminophen, and
corticosteroids. Discontinue SYLVANT if the patient does not tolerate the
infusion following these interventions. [see Adverse Reactions (6)].

Administer SYLVANT in a setting that provides resuscitation equipment,
medication, and personnel trained to provide resuscitation.

Gastrointestinal (GI) Perforation - Use with caution in patients who may be at
increased risk for GI perforation. Promptly evaluate patients presenting with
symptoms that may be associated or suggestive of GI perforation.

Adverse Reactions - The most common adverse reactions (>10% compared to
placebo) in the clinical trial were pruritus, increased weight, rash,
hyperuricemia, and upper respiratory tract infection.

Drug Interactions - Cytochrome P450 (CYP450) Substrates - Upon initiation or
discontinuation of SYLVANT, in patients being treated with CYP450 substrates
with narrow therapeutic index, perform therapeutic monitoring of effect (e.g.,
warfarin) or drug concentration (e.g. Cyclosporine or theophylline) as needed
and adjust dose. Exercise caution when SYLVANT is co‑administered with CYP3A4
substrate drugs where a decrease in effectiveness would be undesirable (e.g.,
oral contraceptives, lovastatin, atorvastatin).

More information about SYLVANT will be available soon at
Please see U.S. full Prescribing Information.

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
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In oncology, our goal is to fundamentally alter the way cancer is understood,
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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 regarding SYLVANT^TM
(siltuximab). 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 Biotech, Inc. and/or Johnson &
Johnson. Risks and uncertainties include, but are not limited to: challenges
inherent in new product development, including obtaining regulatory approvals
and successfully marketing and selling products; competition, including
technological advances, new products and patents attained by competitors;
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distress of purchasers of health care products and services; changes to
governmental laws and regulations and domestic and foreign health care
reforms; and general industry conditions including trends toward health care
cost containment. A further list and description of these risks,
uncertainties and other factors can be found in Johnson & Johnson's Annual
Report on Form 10-K for the fiscal year ended December 29, 2013, including in
Exhibit 99 thereto, and our subsequent filings with the Securities and
Exchange Commission. Copies of these filings are available online at, or on request from Johnson & Johnson. None of the
Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any
forward-looking statement as a result of new information or future events or


^1 SYLVANT™ (siltuximab) Prescribing Information. April 2014.
^2 American Cancer Society. Castleman disease. Last updated June 2012.
Available from:
Accessed April 2014.
^3 Peterson, B. Multicentric Castleman's disease. Seminars in Oncology.
1993;20(6):636-47. Available from:
Accessed April 2014.
^4 Greiner, T. Atypical Lymphoproliferative Diseases. Hematology Am Soc
Hematol Educ Program. 2000:133-146. Available from: Accessed April 2014.
^5 Van Rhee F et al. Castleman Disease in the 21st Century: An Update on
Diagnosis, Assessment, and Therapy. Clinical Advances in Hematology &
Oncology. 2010;8(7):486-98.
^6 Mehra M et al. Use of a Claims Database to Characterize and Estimate the
Incidence of Castleman's Disease. Poster presented at: 54^th American Society
of Hematology (ASH) Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta,
^7 El-Osta HE, Kurzrock R. Castleman's disease: from basic mechanisms to
molecular therapeutics. Oncologist. 2011;16(4):497-511.
^8 Wong RS et al. A Multicenter, Randomized, Double-Blind, Placebo-Controlled
Study Of The Efficacy and Safety Of Siltuximab, An Anti-Interleukin-6
Monoclonal Antibody, In Patients With Multicentric Castleman's Disease. Oral
presentation presented at: 55^th American Society of Hematology (ASH) Annual
Meeting; Dec. 7-11, 2013; New Orleans, LA.

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