The FDA has approved the use of daratumumab (Darzalex, Genmab) in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The supplemental biologics license application (sBLA) for this indication was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., in November 2017. The FDA subsequently granted priority review to the sBLA, with a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2018. In August 2012, Genmab granted Janssen Biotech, Inc., an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.
The approval was based on data from the phase 3 ALCYONE study that showed a reduction of the risk of disease progression or death by 50% (hazard ratio, 0.50; 95% confidence interval, 0.38–0.65; P < 0.0001) in patients with newly diagnosed multiple myeloma ineligible for ASCT when daratumumab is combined with VMP. The safety of daratumumab combination therapy was consistent with the known safety profiles of daratumumab monotherapy and of therapy with bortezomib, melphalan, and prednisone, respectively.
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells. It is the third most common blood cancer in the U.S., after leukemia and lymphoma. Approximately 30,770 new patients are expected to be diagnosed with multiple myeloma and approximately 12,770 people are expected to die from the disease in the U.S. in 2018. Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015. While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems, or infections.
In addition to the new expanded indication, daratumumab injection for intravenous infusion is FDA-approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy 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.
Daratumumab is the first monoclonal antibody to receive FDA approval to treat multiple myeloma and is the first human CD38 monoclonal antibody to reach the market.
Source: Genmab; May 8, 2018.