Seattle Genetics Reports Durable Objective Responses With SGN-35 In Lymphoma - American Society Of Hematology 50th Annual Meeting

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Lymphology/Lymphedema;  Blood / Hematology;  Cancer / Oncology
Article Date: 08 Dec 2008 - 4:00 PDT

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Seattle Genetics, Inc. (Nasdaq: SGEN) today reported data from a phase I clinical trial of SGN-35, an antibody-drug conjugate (ADC), demonstrating multiple complete and partial responses at well-tolerated doses in patients with relapsed or refractory Hodgkin lymphoma and other CD30-positive hematologic malignancies. The data were presented during the American Society of Hematology (ASH) 50th Annual Meeting in San Francisco, California. Based on data from the phase I study, the company is finalizing its U.S. registration pathway and plans to initiate pivotal trials of SGN-35 in the first half of 2009.

Out of 44 evaluable patients treated with SGN-35, 17 patients achieved objective responses, including nine complete responses and eight partial responses. Eighteen additional patients had stable disease and nine patients progressed. The median duration of response was 22 weeks, with 11 responses still ongoing. Across all dose levels, 86 percent of the 42 patients who had at least one post-baseline assessment achieved reductions in tumor volume. Among 28 evaluable patients treated at doses of 1.2 milligrams per kilogram (mg/kg) and higher, 54 percent achieved an objective response, including 32 percent with complete responses. Furthermore, 93 percent of these patients achieved tumor reductions, and their median progression-free survival was greater than six months.

"Patients with Hodgkin lymphoma who relapse following stem cell transplant have limited therapeutic options, and those who relapse within six months have a short predicted survival," said Anas Younes, M.D., Professor of Medicine and Director, Clinical and Translational Research in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, and presenting investigator of the phase I study. "These phase I data are encouraging, and provide evidence that SGN-35 may offer an important new therapeutic option for patients in this setting."

SGN-35 is an ADC comprising an anti-CD30 antibody attached by an enzyme-cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in a targeted cell-killing effect.

"These promising data, including tolerability profile, response rate and durability of responses, suggest that SGN-35 has meaningful therapeutic potential, and we believe it warrants our aggressive development plans," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "We are positioning the program for pivotal trials to begin in the first half of 2009."

SGN-35 Phase I Study

Data from 45 patients treated on the single-arm, dose-escalation study of SGN-35 were presented, including 42 with Hodgkin lymphoma, two with systemic anaplastic large cell lymphoma (ALCL) and one with angioimmunoblastic T-cell lymphoma. Cohorts of patients received doses of SGN-35 every three weeks, escalating from 0.1 mg/kg to 3.6 mg/kg. The median age of patients was 36 years. Enrolled patients had received a median of three prior chemotherapy regimens and 73 percent had received a prior autologous stem cell transplant.

SGN-35 was generally well tolerated. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, diarrhea and nausea. The maximum tolerated dose was defined as 1.8 mg/kg administered every three weeks.

A downloadable copy of Seattle Genetics' SGN-35 poster is available from the "Technology" section of the company's website at www.seattlegenetics.com.

About CD30-Positive Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. A defining attribute of the Reed-Sternberg cell is its expression of the CD30 antigen. According to the American Cancer Society, approximately 8,200 cases of Hodgkin lymphoma will be diagnosed in the United States during 2008. An additional 2,000 to 3,000 patients per year in the United States are diagnosed with ALCL, a T-cell non-Hodgkin lymphoma that expresses the CD30 antigen.

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 SGN-35 and plans for future clinical trials. 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 SGN-35 advances in clinical trials, such as patients exhibiting progressive disease or severe adverse events. In addition, our regulatory plans may change as a result of consultation with the FDA or additional information from our clinical trials. 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.