Seattle Genetics Reports Objective Responses with Dacetuzumab in Phase II Non-Hodgkin Lymphoma Trial
Preclinical data demonstrate enhanced activity of dacetuzumab combined with Rituxan
SEATTLE--(BUSINESS WIRE)--Dec 6, 2008 - Seattle Genetics, Inc. (Nasdaq: SGEN) today reported data from a phase II single-agent clinical trial of dacetuzumab (SGN-40) demonstrating objective responses at well-tolerated doses in heavily pre-treated patients with diffuse large B-cell lymphoma (DLBCL), an aggressive type of non-Hodgkin lymphoma. Data were also presented from preclinical studies of dacetuzumab plus Rituxan® (rituximab) indicating enhanced activity of the combination regimen. These findings were presented during the American Society of Hematology (ASH) 50th Annual Meeting in San Francisco, California.
Dacetuzumab is a humanized monoclonal antibody that targets the CD40 antigen, which is expressed on most B lineage hematologic malignancies, as well as some solid tumors. Seattle Genetics is developing dacetuzumab under a worldwide collaboration agreement with Genentech, Inc.
“The data from this phase II clinical trial are consistent with the activity and tolerability profile observed in our phase I study and reinforce our enthusiasm about the potential of dacetuzumab for the treatment of DLBCL,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. “Ongoing clinical development activities are focused on combining dacetuzumab with standard therapies, including three clinical trials in non-Hodgkin lymphoma. Our preclinical data demonstrate the enhanced efficacy of dacetuzumab when used in combination with Rituxan.”
Seattle Genetics and Genentech are conducting a joint development plan that includes five phase Ib-IIb clinical trials of dacetuzumab in combination with standard therapeutic regimens for the treatment of multiple myeloma and non-Hodgkin lymphoma. Two of these combination studies are in DLBCL, including a phase Ib study of dacetuzumab in combination with Rituxan and Gemzar® (gemcitabine) for patients with relapsed DLBCL and a phase IIb study of dacetuzumab in combination with R-ICE (Rituxan, ifosfamide, carboplatin and etoposide) for second-line DLBCL (SeaGen MARINER trial). Data from these trials are expected in 2009 and 2010, respectively.
Phase II Study Design and Results
Data were reported from the single-arm, single-agent study of dacetuzumab in 46 patients with DLBCL (Abstract #1000). Patients were heavily pre-treated, with a median of four prior systemic therapies. The median age of enrolled patients was 72. Patients received six doses of dacetuzumab over five weeks, with an intra-patient dose escalation up to 8 milligrams per kilogram (mg/kg).
Objective responses were observed in four out of 38 patients evaluable for response, including two complete remissions and two partial remissions, for an overall response rate of 10 percent. The duration of objective responses ranged from 78 days to greater than 271 days. Ten additional patients had stable disease and approximately one-third of all patients had reduction in tumor size.
Dacetuzumab was generally well tolerated. The most common adverse events were fatigue, headache and chills.
Preclinical ASH Abstracts
Seattle Genetics reported preclinical data demonstrating the improved efficacy of the combination of dacetuzumab and Rituxan compared to the activity of either monoclonal antibody alone in models of non-Hodgkin lymphoma. The data suggest that this is due to the distinct apoptotic signaling pathways activated by these antibodies, in addition to their intrinsic effector function activities (Abstract #1583).
Genentech presented research on a gene signature designed to correlate dacetuzumab treatment with antitumor activity. In non-Hodgkin lymphoma cell lines, the gene signature discriminated between cells that were sensitive or resistant to dacetuzumab with a high degree of accuracy (Abstract #1593). Evaluation of the potential correlation between the diagnostic gene signature and antitumor response in patients with non-Hodgkin lymphoma is ongoing.
About Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) represents a diverse group of cancers that develop in the lymphatic system and are characterized by uncontrolled growth and accumulation of abnormal lymphocytes. Lymphocytes are a type of white blood cells that are responsible for defending the body against infection. The most common forms of NHL are follicular (slow growth) and diffuse large B-cell lymphoma (a faster growing subtype).
Under the terms of the collaboration agreement with Genentech, Seattle Genetics received an upfront payment of $60 million in February 2007, and is entitled to receive potential milestone payments exceeding $800 million and escalating double-digit royalties starting in the mid-teens on sales of dacetuzumab. Seattle Genetics also has an option to co-promote dacetuzumab in the United States. To date, Seattle Genetics has received a total of $20 million in milestone payments from Genentech associated with dacetuzumab clinical trial initiations. In addition, Genentech funds research, development, manufacturing and commercialization expenses for dacetuzumab, including reimbursing Seattle Genetics for costs incurred in connection with activities it performs under the collaboration.
About Seattle Genetics
Seattle Genetics is a clinical stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease. The company has four product candidates in ongoing clinical trials: dacetuzumab (SGN-40), lintuzumab (SGN-33), SGN-35 and SGN-70. Dacetuzumab is being developed under a worldwide collaboration with Genentech. In addition, the company has developed proprietary antibody-drug conjugate (ADC) technology comprising highly potent synthetic drugs and stable linkers for attaching the drugs to monoclonal antibodies. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Genentech, Bayer, CuraGen, Progenics, Daiichi Sankyo and MedImmune, a subsidiary of AstraZeneca, as well as an ADC co-development agreement with Agensys, a subsidiary of Astellas Pharma. More information can be found at www.seattlegenetics.com.
Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the potential therapeutic benefit of dacetuzumab. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks related to adverse clinical results as dacetuzumab advances in clinical trials, such as patients exhibiting progressive disease or severe adverse events. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's filings with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contact: Seattle Genetics
Peggy Pinkston, 425-527-4160
Posted: December 2008