Janssen announced the U.S. Food and Drug Administration (FDA) has approved DARZALEX (daratumumab) in combination with VELCADE (bortezomib), a proteasome inhibitor (PI); melphalan, an alkylating agent; and prednisone – VMP – for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). DARZALEX is the first monoclonal antibody approved for newly diagnosed patients with this disease. Clinical trial results showed DARZALEX in combination with VMP reduced the risk of disease progression or death by 50 percent compared to treatment with VMP alone.
"This approval is significant as we now have the first antibody-based regimen for treating newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant," said Andrzej Jakubowiak, M.D., Ph.D., Director of the Multiple Myeloma Program at University of Chicago Medical Center, Chicago, Illinois and a DARZALEX clinical study investigator. "In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response."
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The FDA approval of DARZALEX in combination with VMP is supported by data from the randomized, open-label, multicenter Phase 3 ALCYONE (MMY3007) study, recently published in the New England Journal of Medicine. The combination of DARZALEX with VMP reduced the risk of disease progression or death by 50 percent, compared to treatment with VMP alone (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p
Treatment with DARZALEX in combination with VMP significantly improved overall response rates (91 vs. 74 percent) compared to VMP alone.1 Additionally, measures of stringent complete response (18 vs. 7 percent), complete response or better (43 vs. 24 percent) and very good partial response or better (71 vs. 50 percent) all showed marked improvement. Patients receiving DARZALEX in combination with VMP achieved a more than three-fold increase in the minimal residual disease (MRD) negativity rate (22 vs. 6 percent) compared to those who received VMP alone.
In the ALYCONE study, the most frequent adverse reactions (>20 percent) with at least 5 percent greater frequency in the DARZALEX-VMP arm were upper respiratory tract infection (48 vs. 28 percent), infusion reactions (28 vs. 0 percent) and peripheral edema (21 vs. 14 percent). Serious adverse reactions with at least a 2 percent greater incidence in the DARZALEX-VMP arm vs. VMP were pneumonia (11 vs. 4 percent), upper respiratory tract infection (5 vs.1 percent) and pulmonary edema (2 vs. 0 percent). The most common Grade 3/4 treatment-emergent hematology laboratory abnormalities for DARZALEX-VMP vs. VMP were lymphopenia (58 vs. 53 percent), neutropenia (44 vs. 43 percent) and thrombocytopenia (38 vs. 42 percent). The warnings and precautions for DARZALEX include infusion reactions, interference with cross-matching and red blood cell antibody screening, neutropenia and thrombocytopenia (see Important Safety Information).
This FDA approval marks the fifth indication for DARZALEX, the first CD38-directed antibody approved anywhere in the world and the first antibody approved for newly diagnosed patients with multiple myeloma who are transplant ineligible. DARZALEX was first approved by the FDA in November 2015 as a monotherapy for 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. DARZALEX received additional approvals in November 2016 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 June 2017, DARZALEX received approval 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 PI.