Double, double; myeloma in trouble?

COPENHAGEN, Denmark—Genmab A/S has announced preliminary results from the Phase 2 study of daratumumab in double refractory multiple myeloma conducted by its collaboration partner Janssen Biotech Inc. The overall response rate (ORR) in the study was 29.2 percent in the 16 mg/kg dosing group, and the median duration of response was 7.4 months as determined by an independent review committee.

The study evaluated multiple myeloma patients who have received at least three different lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent (ImiD), or who are double refractory to a proteasome inhibitor and an IMiD. (Examples of proteasome inhibitors are bortezomib or carfilzomib, and examples of IMiD agents are pomalidomide or lenalidomide.) This is the indication for which daratumumab was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in May 2013. In August 2012, Genmab granted Janssen Biotech an exclusive worldwide license to develop and commercialize daratumumab.

“We are very pleased with these positive results in this study of daratumumab as a monotherapy for the treatment of double refractory multiple myeloma,” said Dr. Jan van de Winkel, CEO of Genmab. “We look forward to presenting additional data of this trial at a key upcoming medical conference this year.”

This two-part study enrolled 124 patients. Part one of the study defined an optimal daratumumab regimen going forward, while part two was an expansion, based on the optimal regimen determined in the first part. 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 ORR and to further characterize the safety of daratumumab as a single agent.

Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity, which is in clinical development for multiple myeloma. Daratumumab targets the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma.

Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated human antibody therapeutics for the treatment of cancer. Founded in 1999, the company currently has one marketed antibody, Arzerra (ofatumumab), for the treatment of certain chronic lymphocytic leukemia indications. Additionally, Genmab has a clinical pipeline with both late- and early-stage programs and an innovative preclinical pipeline.

Genmab’s technology base consists of validated and proprietary next-generation antibody technologies—the DuoBody platform for generation of bispecific antibodies and the HexaBody platform that creates effector function-enhanced antibodies. The HexaBody platform strengthens the killing ability of antibodies while retaining regular structure and specificity. The technology has the potential to enhance antibody therapeutics for a broad range of applications in cancer and infectious diseases.

The DuoBody platform is a platform for the discovery and development of bispecific antibodies that may improve antibody therapy of cancer, autoimmune, infectious and central nervous system disease. Bispecific antibodies bind to two different epitopes either on the same or on different targets (also known as dual-targeting), which may improve the antibodies’ specificity and efficacy in inactivating the disease target cells. DuoBody molecules are reportedly unique in combining the benefits of bispecificity with the strengths of conventional antibodies, which allows DuoBody molecules to be administered and dosed as other antibody therapeutics.

The Genmab UniBody technology creates a stable, smaller antibody format. UniBody molecules will inhibit or silence cells, but not kill them, which could be an advantage in the treatment of certain diseases such as asthma or allergies. Genmab’s deep antibody expertise is expected to provide a stream of future product candidates. Partnering of selected innovative product candidates and technologies is a key focus of Genmab’s strategy, and the company has alliances with top tier pharmaceutical and biotechnology companies.