Daratumumab (HuMax®-CD38)

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, and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.  

Daratumumab is approved in the United States 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. DARZALEX is also approved in Europe 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 May 2013, daratumumab received Fast Track Designation and Breakthrough Therapy Designation from the US FDA 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.  In July 2016, daratumumab was granted a second Breakthrough Therapy Designation 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.  Breakthrough Therapy Designation is a program intended to expedite the development and review of drugs to treat serious or life-threatening diseases in cases where preliminary clinical evidence shows that the drug may provide substantial improvements over available therapy. Daratumumab has also received Orphan Drug Designation from the US FDA and the EMA for the treatment of multiple myeloma.

Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing. 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, NKT-cell lymphoma, amyloidosis and solid tumors.  

Genmab announced a global license and development agreement for daratumumab with Janssen Biotech, Inc. in August 2012.  The agreement became effective in September 2012.

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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 IMiDs, have poor prognoses and few treatment options.6

Daratumumab (HuMax®-CD38) is being investigated in studies in multiple indications. For more information on these studies, visit clinicaltrials.gov. Additional studies are planned.

1 American Cancer Society. "Multiple Myeloma Overview." Available
at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2015.

2 National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed September 2015.

3 American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed September 2015.

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 September 2015.

5  American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed August 2015.

6 Janssen JH, et al. Blood. 2012; 120.2974.

 

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Natural killer / T-cell lymphoma (NKTCL), Nasal Type is a type of non-Hodgkin’s lymphoma, which is almost always associated with Epstein-Barr virus. Up to 75% of cases develop in the upper aerodigestive tract, most commonly in the nasal cavity. NKTCL is the most common type of peripheral T-cell lymphoma in many Asian countries, though disease incidence is still rare. The median age of presentation is 40 to 50 years old, but it may occur at any age. Early-stage localized nasal disease is highly curable with combination therapy, though the optimal treatment is as yet undefined.

Source:  http://www.cancernetwork.com/leukemia-lymphoma/current-management-nasal-nkt-cell-lymphoma

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Amyloidosis is a disease that occurs when amyloid proteins, which are abnormal proteins that accumulate in tissues and organs. When the amyloid proteins cluster together they form deposits which damages the tissues and organs. Amyloidosis most frequently affects the kidneys, heart, nervous system, liver and digestive tract. There is currently no cure for amyloidosis. It can be treated with chemotherapy, dexamethasone, stem cell transplants and supportive therapies1.

1 Mayo Clinic website: www.mayoclinic.com/health/amyloidosis/DS00431

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Myelodysplastic syndromes (MDS) are a group of myeloid malignancies characterized by abnormal development of blood cells within the bone marrow1. MDS are diagnosed in more than 10,000 people in the US each year2. MDS are more common in men and older people, with a median age at diagnosis of approximately 703. The different types of MDS are diagnosed based on certain changes in the blood cells and bone marrow. There are currently three types of standard treatment for MDS; supportive care, which may include transfusions, erythropoiesis-stimulating agents and antibiotic therapy; drug therapy with drugs such as lenalidomide, immunosuppressive therapy, azacitidine and decitabine and chemotherapy; chemotherapy with stem cell transplant4.

1 NIH: https://www.cancer.gov/types/myeloproliferative/hp/myelodysplastic-treatment-pdq
2 Ma X, Does M, Raza A, et al.: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109 (8): 1536-42, 2007
3 Sekeres MA, Schoonen WM, Kantarjian H, et al.: Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst 100 (21): 1542-51, 2008.
4 NIH: https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq#section/_49

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