- Phase III MAIA study of daratumumab in combination with lenalidomide and dexamethasone in front line multiple myeloma met the primary endpoint (PFS) at a pre-planned interim analysis demonstrating the superiority of DRd over Rd
- Independent Data Monitoring Committee recommends releasing the interim analysis results and to follow patients for survival and long-term safety
- Data will be discussed with health authorities to prepare for regulatory filings
Copenhagen, Denmark; October 29, 2018 – Genmab A/S (Nasdaq Copenhagen: GEN) announced today topline results from the Phase III MAIA study (MMY3008) of daratumumab in combination with lenalidomide and dexamethasone (DRd) versus Rd alone as treatment for newly diagnosed patients who are not candidates for high dose chemotherapy and autologous stem cell transplant (ASCT).
The study met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.55 (95% CI 0.43 – 0.72), p < 0.0001) resulting in a 45% reduction in the risk of progression or death in patients treated with DRd. The median PFS for patients treated with daratumumab in combination with Rd has not been reached, compared to an estimated median PFS of 31.9 months for patients who received Rd alone.
Overall, the safety profile of daratumumab in combination with Rd is consistent with both the known safety profiles of the Rd regimen and daratumumab.
Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended releasing the interim analysis results. Further analysis of the safety and efficacy data is ongoing and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss the potential for a regulatory submission for this indication with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.
“We are highly encouraged by this data as this is the fifth randomized study showing a profound benefit when adding daratumumab to standard of care treatments in multiple myeloma, and the second showing efficacy for patients with newly diagnosed multiple myeloma who are not eligible for ASCT. As such this data increases our hope that daratumumab may one day help even more patients at the outset of treatment of this disease,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
Today’s news does not impact Genmab’s 2018 financial guidance.
About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide is administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue Rd until disease progression or unacceptable toxicity. The primary endpoint of the study is PFS.
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide is administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue Rd until disease progression or unacceptable toxicity. The primary endpoint of the study is PFS.
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 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 2018.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would 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
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 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 2018.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would 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
About DARZALEX® (daratumumab)
DARZALEX® (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.
DARZALEX® (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. 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. Daratumumab triggers a person’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 (programmed cell death).6,7,8,9,10
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.
Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in combination with the DuoBody logo®; HexaBody®; HexaBody in combination with the HexaBody logo®; DuoHexaBody™; HexElect™; and UniBody®. Arzerra®is a trademark of Novartis AG or its affiliates. DARZALEX® is a trademark of Janssen Pharmaceutica NV.
1 American Cancer Society. “Multiple Myeloma Overview.” Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016.
2 National Cancer Institute. “A Snapshot of Myeloma.” Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016.
3 American Cancer Society. “What are the key statistics about multiple myeloma?” http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed March 2018
4 GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed June 2016.
5 American Cancer Society. “How is Multiple Myeloma Diagnosed?” http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016.
6 DARZALEX Prescribing information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
7 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
8 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.
9 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.
10 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012; 120(21): abstract 2974.
2 National Cancer Institute. “A Snapshot of Myeloma.” Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016.
3 American Cancer Society. “What are the key statistics about multiple myeloma?” http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed March 2018
4 GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed June 2016.
5 American Cancer Society. “How is Multiple Myeloma Diagnosed?” http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016.
6 DARZALEX Prescribing information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
7 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
8 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.
9 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.
10 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012; 120(21): abstract 2974.