Photo courtesy of Janssen
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for daratumumab (Darzalex), a first-in-class monoclonal antibody targeting CD38.
The recommended indication for daratumumab is as monotherapy for adults with relapsed and refractory multiple myeloma (MM).
The patients must have progressed on their last therapy and have received treatment with both a proteasome inhibitor and an immunomodulatory agent.
The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for medicines in the European Economic Area.
The European Commission’s final decision on daratumumab is anticipated in the coming months.
About conditional authorization
A product may receive conditional marketing authorization if the CHMP finds that, although comprehensive clinical data on the safety and efficacy of the product are not available, all of the following requirements are met:
- The risk-benefit balance of the product is positive
- The company developing the product will likely be in a position to provide comprehensive clinical data in the future
- Unmet medical needs will be fulfilled
- The benefit to public health of the immediate availability of the product outweighs the risk inherent in the fact that additional data are still required.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder will be required to complete ongoing studies or to conduct new studies with a view to confirming that the benefit-risk balance of a product is positive. In addition, specific obligations may be imposed in relation to the collection of pharmacovigilance data.
About daratumumab
Daratumumab is the first CD38-directed monoclonal antibody recommended for approval in Europe. It works by binding to CD38, a signaling molecule highly expressed on the surface of MM cells regardless of stage of disease.
In binding to CD38, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple, immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis.
The CHMP’s positive opinion of daratumumab was based on a review of data from the phase 2 SIRIUS study, the phase 1/2 GEN501 study, and 3 additional supportive studies.
The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.
The results suggested daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%. Most adverse events in this study were grade 1 or 2, although serious events did occur.
The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 patients received the drug at 16 mg/kg.
Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.
Findings from a combined efficacy analysis of the GEN501 and SIRIUS trials demonstrated that, after a mean follow-up of 14.8 months, the estimated median overall survival for patients who received single-agent daratumumab at 16 mg/kg was 20 months.
Five phase 3 clinical studies with daratumumab in MM patients—in relapsed and frontline settings—are ongoing. Additional studies are ongoing or planned to assess the drug’s potential in other malignant and pre-malignant diseases in which CD38 is expressed.
Janssen has exclusive worldwide rights to the development, manufacturing, and commercialization of daratumumab for all potential indications. Janssen licensed daratumumab from Genmab A/S in August 2012.
