On January 7, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported The Lancet has published data from the Phase II study (Sirius MMY2002) of daratumumab in patients with relapsed and refractory multiple myeloma (Press release, Genmab, JAN 7, 2016, View Source [SID:1234508679]). Schedule your 30 min Free 1stOncology Demo! Patients that received 16 mg/kg of daratumumab had a median of five prior lines of therapy and 95.3% were refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs, which are current standard of care treatments for multiple myeloma. The data showed a 29.2% overall response rate (31 of 106), including three stringent complete responses, ten very good partial responses, and 18 partial responses in patients treated with 16 mg/kg of daratumumab. The median time to response was one month among patients who responded to treatment. Median duration of response was 7.4 months, and median progression free survival was 3.7 months. The 12-month overall survival rate was 64.8% and at a subsequent cutoff, median overall survival was 17.5 months. Daratumumab was well tolerated, with fatigue (40%) and anemia (33%) of any grade as the most common adverse events (AEs). No drug-related AEs led to treatment discontinuation.
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"Data from the daratumumab Sirius study illustrates the significant potential of daratumumab in patients with multiple myeloma who have undergone multiple rounds of prior treatment. Data from the study, now published in The Lancet, was the basis for the approval of daratumumab in heavily pre-treated or double refractory multiple myeloma by the U.S. FDA," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
In November 2015, the U.S. Food and Drug Administration (FDA) approved DARZALEX (daratumumab) injection for intravenous infusion for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 A marketing application with data from the Sirius study and data from four other studies was submitted to the European Medicines Agency (EMA) by Janssen in September 2015 and was subsequently granted accelerated assessment.
About the Study (Sirius MMY2002)
This two-part study enrolled 124 patients who have received at least three prior lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent. Examples of proteasome inhibitors are bortezomib or carfilzomib and examples of immunomodulatory agents are pomalidomide or lenalidomide. Part 1 defined an optimal daratumumab regimen going forward, while part 2 was an expansion, based on the optimal regimen determined in Part 1. The primary objective of the study was to define the optimal dose and dosing schedule, to determine the efficacy of two treatment regimens of daratumumab as measured by overall response rate (ORR), and to further characterize the safety of daratumumab as a single agent.
About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 124,225 people will be diagnosed and 87,084 will die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including PIs or immunomodulatory agents, have poor prognoses and few treatment options.6
About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.10 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,10 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,10 antibody-dependent cellular phagocytosis8,11 and antibody-dependent cellular cytotoxicity.7,10 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and a subset of regulatory T cells (Tregs) both of which express CD38. These reductions in MDSCs and Tregs were paralleled by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.10
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma.