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81% of evaluable patients achieved reductions in tumor volume
SEATTLE, WA, USA | Jun 3, 2008 | Seattle Genetics, Inc. (Nasdaq: SGEN) today announced positive data from a phase I clinical trial of SGN-35, an antibody-drug conjugate (ADC), demonstrating multiple objective responses at well-tolerated doses in patients with Hodgkin lymphoma and other CD30-positive hematologic malignancies. The data were presented during a poster discussion session at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting being held in Chicago, Illinois.
Out of 38 patients treated with SGN-35 who were evaluable for response, twelve patients achieved objective responses, including five complete responses and seven partial responses. Fifteen additional patients had stable disease and eleven had progressive disease. Eighty-one percent of the 37 patients who had at least one post-baseline assessment achieved reductions in tumor volume. At doses of 1.2 milligrams per kilogram (mg/kg) and higher, 45 percent of evaluable patients (10 out of 22) achieved an objective response and 23 percent (5 out of 22) achieved a complete response. Response duration of greater than six months has been observed in several patients still on study. The trial is ongoing.
"There are no approved therapies for patients with relapsed or refractory Hodgkin lymphoma, and treatment options are especially limited for recurrent disease following stem cell transplant," 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. "Patients who relapse within six months of a stem cell transplant have a short predicted survival. These phase I data indicate that SGN-35 may provide an important new therapeutic option for patients in this setting who are in need of more effective and better tolerated therapies."
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.
"We are extremely pleased by our clinical findings with SGN-35, notably its ability to induce complete and partial responses at well-tolerated doses, and believe the data support aggressive development of this ADC," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "In addition, these clinical data demonstrate the therapeutic potential of antibodies empowered by our ADC technology. We are designing pivotal trials with SGN-35 and expect to finalize our development plans, including registration pathway, in the second half of 2008."
Based on market research, Seattle Genetics believes that there are several thousand newly relapsed or refractory lymphoma patients in the United States each year who would be eligible for treatment with SGN-35, and that the United States prevalence population of these patients is approximately 10,000 to 12,000 individuals. The company projects that the worldwide annual market potential for SGN-35 in relapsed or refractory lymphoma is $300 million to $400 million with additional potential in the front line setting. SGN-35 has received orphan drug designation from the FDA for the treatment of Hodgkin lymphoma.
SGN-35 Phase I Study Design and Results
Data from 39 patients treated on the single-arm, dose-escalation study of SGN-35 were presented at ASCO, including 36 with Hodgkin lymphoma, two with systemic anaplastic large cell lymphoma (ALCL) and one with angioimmunoblastic T-cell lymphoma. The median age of patients was 36 years. Cohorts of patients received doses of SGN-35 every three weeks, escalating from 0.1 mg/kg to 3.6 mg/kg. Enrolled patients had received a median of three prior chemotherapy regimens and 74 percent had received a prior autologous stem cell transplant.
Pharmacokinetic findings indicate dose-related increases in exposure to SGN-35 and minimal immunogenicity. The majority of adverse events have been Grade 1 and 2, including fatigue, cough and nausea. One patient at the highest dose of 3.6 mg/kg developed fever, neutropenia and sepsis, and died 14 days after the first dose of SGN-35.
Based on the encouraging phase I results, Seattle Genetics initiated a second phase I trial to further explore the therapeutic potential of SGN-35. The trial is designed to initially evaluate escalating single-agent doses of SGN-35 administered weekly to patients with relapsed or refractory CD30-positive hematologic malignancies, including Hodgkin lymphoma. Following the monotherapy portion of the study, the trial will continue with an investigation of SGN-35 in combination with Gemzar(R) (gemcitabine), a chemotherapy agent commonly used in the treatment of Hodgkin lymphoma.
A downloadable copy of the ASCO 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 anaplastic large cell lymphoma (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 a worldwide collaboration with Genentech for SGN-40. Seattle Genetics also has two other product candidates in ongoing clinical trials: SGN-33 and SGN-35. 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 and MedImmune, a wholly-owned subsidiary of AstraZeneca, as well as an ADC co-development agreement with Agensys, a wholly-owned subsidiary of Astellas Pharma.
SOURCE: Seattle Genetics, Inc. |
