March 21, 2014
Janssen-Cilag International NV (“Janssen”) announced today that The Committee for Medical Products for Human Use (CHMP) of The European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a marketing authorisation for siltuximab for the treatment of adult patients with multicentric Castleman’s disease (MCD) who are HIV-negative and human herpes virus-8 (HHV-8)-negative. If approved, siltuximab would be the first medicine to receive regulatory approval in the EU for treatment of MCD patients.
MCD is a very rare and complex blood disorder with high morbidity. It is a condition in which lymphocytes, a type of white blood cells, 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. Infections, multisystem organ failure, and malignancies including malignant lymphoma are common causes of death in patients with MCD.
The positive opinion of the CHMP is based on a review of data from a multinational, randomised, double-blind, placebo-controlled pivotal study (MCD2001) in 79 patients with MCD, along with data from two non-randomised supportive studies. The MCD2001 study assessed the safety and efficacy of siltuximab plus best supportive care (BSC) compared with placebo plus BSC in patients with MCD who are HIV-negative and HHV-8-negative. The primary endpoint of the study was durable tumour and symptomatic response, defined as tumour response assessed by independent review and complete resolution or stabilisation of prospectively collected MCD symptoms, for at least 18 weeks without treatment failure. Secondary endpoints included additional predefined efficacy measures and safety.
MCD2001 is the first randomised study in MCD. Results showed that more than one-third of patients in the siltuximab arm had a durable tumour and symptomatic response to treatment plus BSC, compared to none of the patients who received placebo plus BSC (34 percent versus 0 percent; p=0.0012; based on central review). The median time to treatment failure was not reached for patients who received siltuximab plus BSC over 48 weeks of treatment; those who received placebo plus BSC experienced treatment failure at a median of 134 days (p=0.0084).
“At Janssen, we are driven by our commitment to patients and to the research and development of innovative products,” saidJane Griffiths, Company Group Chairman of Janssen Europe, the Middle East and Africa (EMEA). “We are therefore very pleased with the CHMP positive opinion and are proud of our work on siltuximab, which has the potential to address an unmet need amongst MCD patients, for whom no approved treatment in the EU currently exists.”
Siltuximab was granted orphan drug status in MCD in both the EU and the United States (U.S.). A final decision for siltuximab is expected from the European Commission within the next three months.
On September 3, 2013, Janssen announced the submission of a Biologic License Application (BLA) to the U.S. Food and Drug Administration (U.S. FDA) 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, which is currently ongoing.
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