A European Medicines Agency (EMA) panel has recommended granting conditional marketing authorization to daratumumab (Darzalex, Janssen Biotech), to be used in the treatment of patients with relapsed and refractory multiple myeloma.
The indication is for patients who have already been treated with a proteasome inhibitor and an immunomodulatory agent and whose disease worsened after treatment.
Daratumumab is the first human anti-CD38 monoclonal antibody to be approved anywhere in the world. CD38 is a surface protein that is expressed by most, if not all, multiple myeloma cells. It is believed that daratumumab induces tumor cell death through multiple immune-mediated mechanisms of action, in addition to apoptosis.
The Committee for Medicinal Products for Human Use (CHMP) reviewed daratumumab under the EMA accelerated assessment program and recommended conditional approval for the drug.
Conditional approval allows the EMA to recommend a medicine for marketing authorization in the interest of public health when the benefit of its immediate availability to patients outweighs the risks inherent in the fact that additional data are still required.
In this case, the CHMP recommendation was made on the basis of results from two studies. In the first, which involved 106 patients who received daratumumab, 29% experienced a complete or partial reduction in their tumor burden, which lasted an average of 7.4 months.
In the second study, which involved 42 patients, 36% experienced a complete or partial reduction in their tumor burden.
Common adverse events include infusion-related reactions, fatigue, nausea, back pain, fever, and cough. Daratumumab can also lead to lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia, and it should not be used during pregnancy. Women who would like to become pregnant should use effective contraception for 3 months after stopping the drug.
Daratumumab was approved in the United States last year on the basis of the same two studies. The product was given priority review and went through the US Food and Drug Administration accelerated approval program. It was granted breakthrough designation and orphan drug status.
As part of the conditional marketing authorization in Europe, the manufacturer must provide results from two phase 3 studies of daratumumab used in combination with standard myeloma treatments (lenalidomide/dexamethasone and bortezomib/dexamethasone).
Both clinical trials are ongoing, and data will be available in the second half of 2017. Until full data are provided, the CHMP will review the benefits and risks of the drug annually to determine whether the conditional marketing authorization can be maintained.
Daratumumab was given an orphan designation from the Committee for Orphan Medicinal Products in 2013.