The primary efficacy endpoint of the study was durable tumor and symptomatic response, defined as partial response or complete response (Cheson criteria) by independent radiological review, and improvement/stabilization in MCD-related symptoms for at least 18 weeks. Secondary endpoints included additional predefined efficacy measures and safety. The primary analysis occurred after the last treated patient completed assessments at 48 weeks.
Baseline MCD symptoms included fatigue (86 percent), malaise (61 percent), night sweats (52 percent), peripheral sensory neuropathy (nerve damage in the peripheral nervous system) (38 percent), anorexia and pruritus (itching) (37 percent each). Median treatment duration was 375 days with siltuximab versus 152 days with placebo, with 64 percent versus 27 percent completing 48 weeks of treatment, respectively.
About Multicentric Castleman
MCD is a rare disorder with high morbidity in which lymphocytes, a certain type of white blood cells, 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.
Signs and symptoms are driven by dysregulated Interleukin-6 (IL-6) production.
Many common symptoms include fever, weakness, fatigue, night sweats, weight loss, loss of appetite, nausea, vomiting and nerve damage that leads to numbness and weakness.
Some symptoms can be life threatening.
Infections, renal failure, and malignancies including malignant lymphoma and Kaposi's sarcoma are common causes of death in patients with MCD.
Currently, there are no approved treatments in the U.S. or EU for MCD.
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.
Currently, the focus of care is to reduce lymph node masses 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.
Castleman's disease is formally diagnosed through a biopsy.
The number of people diagnosed with Castleman's disease is unknown, but the disease is known to be rare.
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. Dysregulated, or imbalanced, overproduction of IL-6 from activated B cells in affected lymph nodes has been implicated in the pathogenesis of MCD.
Information about ongoing studies with siltuximab can be found on clinicaltrials.gov.
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 U.S. FDA accepted the submission and granted siltuximab priority review, and the EMA has granted Accelerated Assessment of the MAA for siltuximab. Siltuximab has been granted orphan drug status in MCD in the U.S. and EU. With the regulatory submissions, a Named Patient Program (NPP) was made available in the U.S. for siltuximab to provide pre-approval treatment access to eligible patients with MCD.
About Janssen Research & Development, LLC
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