Johnson & Johnson (NYSE:JNJ) disclosed that FDA accepted and granted Priority Review to a BLA for siltuximab (CNTO 328) to treat multicentric Castleman's disease (MCD) in patients who are HIV-negative and human herpes virus 8 (HHV-8)-negative. The PDUFA date is not disclosed. An MAA is also under accelerated assessment by EMA for the indication. The pharma submitted the applications in September. Multicentric Castleman's disease is a rare type of Castleman's disease that affects more than one group of lymph nodes in different anatomical areas. Castleman's disease is a B cell proliferative disorder that is not malignant but is nonetheless fatal because of systemic inflammation.
J&J also presented data at the American Society of Hematology meeting showing that IV siltuximab every three weeks plus best supportive care (BSC) led to a greater durable tumor and symptomatic response rate, the primary endpoint, vs. placebo plus BSC (34% vs. 0%, p=0.0012) in the Phase II MCD2001 trial to treat MCD. Median time to treatment failure was not reached in the siltuximab arm vs. 134 days in the placebo arm. The double-blind, international trial enrolled 79 patients with multicentric Castleman's disease who are HIV-negative and HHV-8-negative. Siltuximab is a chimeric mAb against IL-6.

Johnson & Johnson’s Janssen unit has filed siltuximab in the US and EU for the treatment of patients with the rare blood disorder, multicentric Castleman disease (MCD). The disorder leads to the over-production of lymphocytes and enlargement of lymph nodes. Siltuximab has orphan drug status in the US and Europe, and if approved would be the first drug specifically for the treatment of MCD.
The market application submitted by Janssen is for the use of siltuximab in patients with MCD who do not have HIV or human herpes virus-8. The monoclonal antibody targets and binds to human IL-6, which has been identified as a critical driver in the pathogenesis of MCD. 
Siltuximab (INN) (also known as CNTO 328, Anti-IL-6 chimeric monoclonal antibody or cCLB8) is a chimeric (made from human and mouse proteins)monoclonal antibody. It binds to interleukin-6.[1] Siltuximab has been investigated for the treatment of metastatic renal cell cancer,[2] prostate cancer,[3] and Castleman's disease,[4][5] among other types of cancer.[6]
It has undergone a phase I clinical trial in Patients With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease.[7]
It gave encouraging results in a small trial for advanced ovarian cancer.[8]
Encouraging results have been reported from a phase II trial for relapsed or refractory multiple myeloma.[9]

References

  1. Jump up^ International Nonproprietary Names for Pharmaceutical Substances (INN, prepublication copy), World Health Organization.
  2. Jump up^ Rossi, J. -F.; Négrier, S.; James, N. D.; Kocak, I.; Hawkins, R.; Davis, H.; Prabhakar, U.; Qin, X.; Mulders, P.; Berns, B. (2010). "A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer". British Journal of Cancer 103 (8): 1154–1162.doi:10.1038/sj.bjc.6605872. PMC 2967052. PMID 20808314. edit
  3. Jump up^ Karkera, J.; Steiner, H.; Li, W.; Skradski, V.; Moser, P. L.; Riethdorf, S.; Reddy, M.; Puchalski, T.; Safer, K.; Prabhakar, U.; Pantel, K.; Qi, M.; Culig, Z. (2011). "The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study".The Prostate 71 (13): 1455–1465. doi:10.1002/pros.21362. PMID 21321981. edit
  4. Jump up^ Van Rhee, F.; Fayad, L.; Voorhees, P.; Furman, R.; Lonial, S.; Borghaei, H.; Sokol, L.; Crawford, J.; Cornfeld, M.; Qi, M.; Qin, X.; Herring, J.; Casper, C.; Kurzrock, R. (2010). "Siltuximab, a Novel Anti-Interleukin-6 Monoclonal Antibody, for Castleman's Disease". Journal of Clinical Oncology 28 (23): 3701–3708. doi:10.1200/JCO.2009.27.2377. PMID 20625121. edit
  5. Jump up^ First IL-6–blocking drug nears approval for rare blood disorder Nature Medicine, October 7, 2013
  6. Jump up^ ClinicalTrials.gov: Siltuximab
  7. Jump up^ "A Safety and Efficacy Study of CNTO 328 in Patients With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease".
  8. Jump up^ "CNTO 328 Shows Promise For Ovarian Cancer In Small Clinical Trial, Say U.K. Scientists.". 2009.
  9. Jump up^ "A phase II multicenter study of CNTO 328, an anti-IL-6 monoclonal antibody, in patients (pts) with relapsed or refractory multiple myeloma (MM)". 2009.