Genmab, the publicly traded, international biotechnology company, has an oncology pipeline that focuses on two classes of drugs: naked antibodies and antibody drug conjugates (ADCs). Its products are being developed in more than 70 active clinical studies, and its lead agent, ofatumumab (Arzerra), was launched after only 8 years in development. Other products undergoing clinical investigation at Genmab include the antibody daratumumab and the ADC HuMax- TF-ADC.
Results from a recent phase III study presented at the 55th American Society of Hematology Annual Meeting in New Orleans, Louisiana, demonstrated improved clinical outcomes when ofatumumab was added to chlorambucil in patients with previously untreated chronic lymphocytic leukemia (CLL). The data showed that median progressionfree survival, overall response rate, complete response rate, and the treatment-free period were all superior with the addition of ofatumumab to chlorambucil compared with chlorambucil alone
Ofatumumab is a monoclonal antibody that targets an antibody determinant (epitope) that’s found on the B-lymphocyte antigen CD20. Ofatumumab attaches to the CD20 molecule, which is found on the surface of B cells. B cells become cancerous in CLL. The CD20 molecule is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin.
Genmab and GlaxoSmithKline comarket ofatumumab. It is approved for patients with CLL who are refractory to fludarabine and alemtuzumab. The FDA recently granted priority review to a supplemental Biologics License Application for ofatumumab in combination with an alkylator-based therapy in treatment-naïve CLL patients who are not eligible for fludarabine-based therapy. A decision on the indication will be made on or before April 19.
The most common adverse reactions reported with ofatumumab are neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common serious adverse reactions seen are infections (including pneumonia and sepsis), neutropenia, and pyrexia.
Ofatumumab is undergoing investigation in other oncology and autoimmune diseases including follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), Waldenström’s Macroglobulinemia, pemphigus vulgaris, and relapsing-remitting multiple sclerosis.
Another monoclonal antibody in Genmab’s pipeline is daratumumab, a human CD38 antibody that is undergoing investigation in multiple myeloma. The drug could also have potential in other hematological malignancies in which CD38 is expressed, including DLBCL, CLL, acute lymphoblastic leukemia, acute myeloid leukemia, follicular lymphoma, and mantle cell lymphoma.
The FDA has granted daratumumab Fast Track designation as a potential treatment in patients with multiple myeloma. It is indicated in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and IMiD.
HuMax-TF-ADC is an ADC that targets tissue factor, a protein involved in tumor signaling and angiogenesis. The conjugate is highly expressed in solid tumors, with rapid internalization. These characteristics make it a viable target for an ADC approach. It is being developed in collaboration with Seattle Genetics. HuMax-TF-ADC is undergoing a phase I dose escalation trial to treat multiple solid tumors.
Genmab’s Oncology Pipeline