Data from Brentuximab Vedotin (SGN-35) Phase I Clinical Trial Published in New England Journal of Medicine
BOTHELL, Wash. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov 3, 2010 - Seattle Genetics, Inc. (Nasdaq: SGEN) and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), today announced that data from a phase I single-agent clinical trial of brentuximab vedotin (SGN-35) will be published in the November 4, 2010 issue of the New England Journal of Medicine. The trial was designed to assess the safety and determine the maximum tolerated dose (MTD) of brentuximab vedotin in patients with CD30-positive hematologic malignancies, including Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Secondary endpoints included evaluation of antitumor activity, pharmacokinetics and immunogenicity. Brentuximab vedotin is a novel antibody-drug conjugate (ADC) targeting CD30, a marker for a number of malignancies including Hodgkin lymphoma and ALCL.
“Brentuximab vedotin induced durable remissions with manageable side effects for a large segment of patients in this phase I experience,” said Anas Younes, M.D., lead author of the publication, an investigator on the trial and Professor of Medicine and Director, Clinical and Translational Research in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “In this study, we were able to identify the MTD and gain an understanding of the safety profile of brentuximab vedotin. There is a high unmet need for patients with Hodgkin lymphoma who relapse following autologous stem cell transplant, where overall survival is only 32 percent at five years. With a median age in the 30s for patients with relapsed Hodgkin lymphoma, these data suggest that brentuximab vedotin may be a promising new option to address the unmet need in these patients.”
Highlights from the phase I trial include:
- Brentuximab vedotin was generally well-tolerated. Adverse events were mostly Grade 1 or 2, with the most common being fatigue, fever, diarrhea, nausea, neutropenia and peripheral neuropathy
- The MTD was 1.8 milligrams per kilogram (mg/kg) every three weeks
- At doses of 1.2 mg/kg and higher, 54 percent of evaluable patients (15 of 28) achieved an objective response per investigator assessment, including 39 percent (11 of 28) complete remissions
- The median duration of response was at least 9.7 months
“These phase I data provided the foundation for our current brentuximab vedotin clinical development program, including our pivotal trial in relapsed or refractory Hodgkin lymphoma and our phase II trial in relapsed or refractory ALCL, from which we recently reported positive top-line data,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. “We remain focused on plans to submit our Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the first half of 2011. In addition, we have a broad clinical development program of ongoing and planned clinical trials to evaluate the use of brentuximab vedotin in earlier lines of Hodgkin lymphoma and ALCL, as well as in other CD30-positive malignancies.”
“We are pleased that these phase I data met the rigorous New England Journal of Medicine standards for publication,” said Nancy Simonian, M.D., Chief Medical Officer of Millennium. “The impressive results from this study and the decision to publish this article reflects the continued interest among the scientific community in brentuximab vedotin.”
Brentuximab Vedotin Phase I Study
In the phase I dose-escalation study, cohorts of patients received a dose of brentuximab vedotin every three weeks, ranging from 0.1 mg/kg to 3.6 mg/kg. Forty-five patients were enrolled, including 42 with Hodgkin lymphoma, two with systemic ALCL and one with CD30-positive angioimmunoblastic T-cell lymphoma. 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.
Of 44 evaluable patients treated with brentuximab vedotin across all dose levels, 39 percent achieved objective responses, including 25 percent complete remissions and 14 percent partial remissions. Forty-three percent of patients had stable disease and 18 percent progressed. Overall, 82 percent of patients had either stable disease or responded to treatment. Tumor-related symptoms were relieved in 81 percent of patients in whom such symptoms were present at baseline.
Across all dose levels, the most common adverse events were typically Grade 1 or 2 in severity, and included fatigue (36 percent), fever (33 percent), and diarrhea, nausea, neutropenia and peripheral neuropathy (22 percent each). Among 12 patients treated at the 2.7 mg/kg dose, three patients had Grade 3 dose-limiting toxicities, including hyperglycemia and unrelated acute renal failure (1 patient each), and febrile neutropenia and unrelated prostatitis (one patient). On the basis of these observations, the MTD was defined as 1.8 mg/kg.
Seattle Genetics and Millennium recently reported positive top-line data from a pivotal trial of brentuximab vedotin for relapsed or refractory Hodgkin lymphoma and a phase II trial for relapsed or refractory ALCL. More complete data from both trials will be presented in oral sessions at the American Society of Hematology (ASH) Annual Meeting, December 4-7, 2010, in Orlando, FL.
About Brentuximab Vedotin
Brentuximab vedotin is an ADC comprising an anti-CD30 monoclonal antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE) utilizing Seattle Genetics' proprietary technology. The ADC employs a novel linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. This approach is intended to spare non-targeted cells and thus may help minimize the potential toxic effects of traditional chemotherapy while allowing for the selective targeting of CD30-expressing cancer cells, thus potentially enhancing the antitumor activity.
In addition to the pivotal Hodgkin lymphoma trial and phase II ALCL trial, Seattle Genetics and Millennium are conducting a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant, a phase II retreatment trial for relapsed patients who previously responded to brentuximab vedotin, and a phase I combination trial for front-line treatment of Hodgkin lymphoma.
About the Seattle Genetics/Millennium Collaboration
Seattle Genetics and Millennium are jointly developing brentuximab vedotin. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.
About Hodgkin Lymphoma and ALCL
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.
Globally, there are more than 30,000 cases of Hodgkin lymphoma diagnosed each year. Although front-line combination chemotherapy can result in durable response rates, up to 30 percent of patients relapse or are refractory to front-line treatment and have few therapeutic options beyond ASCT. ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30.
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 recently reported positive top-line data from both a pivotal Hodgkin lymphoma trial and phase II anaplastic large cell lymphoma trial with its lead product candidate, brentuximab vedotin, and plans to submit a BLA to the FDA in the first half of 2011. Brentuximab vedotin is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has four other clinical-stage programs: SGN-75, ASG-5ME, dacetuzumab (SGN-40) and SGN-70. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium: The Takeda Oncology Company and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets a first-in-class proteasome inhibitor in the US, and has a robust clinical development pipeline of global product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company's research, development and commercialization activities are focused in oncology. Additional information about Millennium and Takeda are available through their respective websites, www.millennium.com and www.takeda.com.
For Seattle Genetics: Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential therapeutic benefit of brentuximab vedotin and plans for submission for regulatory approval to and obtaining regulatory approval from the FDA and the EMA. 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 that the safety and/or efficacy results of the pivotal trial in relapsed or refractory Hodgkin lymphoma and phase II trial in relapsed or refractory ALCL will not be sufficient to gain marketing approval in the United States or any other country, that we will be required to amend our submission for marketing approval or that such submission will be refused. In addition, our regulatory plans may change as a result of consultation with the FDA or EMA. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended June 30, 2010 filed 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.
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Posted: November 2010