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Janssen-Cilag International NV announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a Positive Opinion recommending a conditional marketing authorisation for first-in-class CD38 immunotherapy DARZALEX® (daratumumab) in the European Union. The recommended indication is for monotherapy of adult patients with relapsed and refractory multiple myeloma (MM), whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.1 This application was reviewed under an accelerated assessment by the CHMP, a process reserved for medicinal products expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
MM is a blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.2 In cases of refractory MM, the disease has progressed on or within 60 days of the last therapy.3 The prognosis for patients with relapsed and refractory MM remains poor. For patients with refractory MM, the median overall survival (OS) ranges from nine months to only five months.4
The Opinion of the CHMP was based on a review of data from the Phase II MMY2002 (SIRIUS) study, published in The Lancet,5 the Phase I/II GEN501 study, published in The New England Journal of Medicine,6 and data from three additional supportive studies. These studies included heavily pre-treated patients with relapsed and refractory multiple myeloma who had exhausted other approved treatment options and whose disease was progressive at enrolment. Findings from a combined efficacy analysis of the GEN501 and MMY2002 (SIRIUS) trials demonstrated that after a mean follow-up of 14.8 months, the estimated median OS for single-agent daratumumab (16 mg/kg) in these heavily pre-treated patients was 20 months (95 percent CI, 15-not estimable). The overall response rate (ORR) for the combined analysis was 31%, and 83% of patients achieved stable disease or better.7
Daratumumab is the first CD38-directed monoclonal antibody (mAb) recommended for approval in Europe. It works by binding to CD38, a signalling molecule highly expressed on the surface of multiple myeloma cells regardless of stage of disease. In doing so, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumour cell death through multiple, immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumour cell death via apoptosis (programmed cell death).8–11
“We are committed to delivering innovative new therapies to patients living with complex blood cancers, and have been working closely with the CHMP on the submission of daratumumab to ensure the assessment could be completed under the accelerated timeline,” said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. “We are delighted to receive this Positive Opinion, which brings us one step closer to making daratumumab available to multiple myeloma patients in Europe.”
The CHMP’s Positive Opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorisation for medicines in the European Economic Area. The European Commission’s final decision on daratumumab is anticipated in the coming months.
This announcement follows daratumumab being granted its first regulatory approval by the US Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent, in November 2015 after a four month Priority Review by the FDA.9
Janssen has exclusive worldwide rights to the development, manufacturing and commercialisation of daratumumab for all potential indications. Janssen licensed daratumumab from Genmab A/S in August 2012.