-94 Percent of Patients Had Reductions in Tumor Volume-
-34 Percent of Patients Achieved Complete Remission-
-BLA Submission for Relapsed or Refractory Hodgkin Lymphoma and ALCL Planned in First Quarter of 2011; Planned MAA Submission in First Half of 2011 Under Discussion with European Regulators-
ORLANDO, Fla.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (Nasdaq:SGEN) and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), today announced positive results from the pivotal trial of single-agent brentuximab vedotin (SGN-35) in relapsed or refractory Hodgkin lymphoma. Brentuximab vedotin is an antibody-drug conjugate (ADC) targeted to CD30, a defining marker of Hodgkin lymphoma. The data were featured during a press briefing today at the 52nd American Society of Hematology (ASH) Annual Meeting in Orlando, FL and will be presented during an oral session on Monday, December 6, 2010, at 7:00 a.m. Eastern Time.
Key findings from the trial in 102 relapsed or refractory Hodgkin lymphoma patients included:
- 75 percent of patients achieved an objective response as assessed by an independent central review using the stringent Cheson 2007 criteria, the primary endpoint of the trial.
- 34 percent of patients achieved a complete remission.
- The median duration of response was 29 weeks by independent central review and 47 weeks by investigator assessment.
- Among patients achieving a complete remission, the median duration of response had not yet been reached at a median follow-up of approximately one year.
- Tumor reductions were achieved in 94 percent of patients.
- Brentuximab vedotin treatment was associated with manageable adverse events, with the most common being peripheral sensory neuropathy, fatigue, nausea, upper respiratory tract infection and diarrhea. The most common Grade 3 or higher adverse events were neutropenia, peripheral sensory neuropathy, thrombocytopenia and anemia.
“Up to thirty percent of all patients diagnosed with Hodgkin lymphoma will relapse. These patients have limited treatment options beyond autologous stem cell transplantation and represent a significant unmet medical need,” said Dr. Robert Chen, Assistant Professor, Hematology & Hematopoietic Cell Transplantation at City of Hope. “Based on these data, brentuximab vedotin has the potential to change the treatment paradigm for relapsed or refractory Hodgkin lymphoma patients, and could be the first treatment approved for these patients in more than 20 years.”
“I have rarely seen such response rates in this relapsed or refractory disease population,” said Dr. Andreas Engert, Professor of Internal Medicine, University of Cologne, Germany. “These data highlight brentuximab vedotin as a potential addition to the treatment options for Hodgkin lymphoma patients.”
Based on recent discussions with the U.S. Food and Drug Administration (FDA), Seattle Genetics plans to submit a Biologics License Application (BLA) in the first quarter of 2011 to seek approval for both relapsed or refractory Hodgkin lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Millennium has initiated discussions with European regulators to support the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the first half of 2011. In addition, in early 2011, Seattle Genetics plans to implement a limited patient access program for qualified relapsed or refractory Hodgkin lymphoma and systemic ALCL patients in the United States. Outside of the United States and Canada, brentuximab vedotin will be made available to qualified relapsed or refractory Hodgkin lymphoma and systemic ALCL patients through a Named Patient Program (NPP). An NPP is a compassionate use drug supply program under which medical practitioners can legally supply investigational drugs to their eligible patients.
About the Pivotal Hodgkin Lymphoma Trial (Abstract #283)
The single-arm pivotal trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory, post-autologous stem cell transplant (ASCT) Hodgkin lymphoma patients. Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to 16 total doses. The primary endpoint of the trial was objective response rate as assessed by an independent central review. Response assessments were based on the rigorous and internationally established Revised Response Criteria for Malignant Lymphoma (Cheson, 2007). Secondary endpoints included complete response rate, duration of response, progression-free survival, overall survival and tolerability.
The median age of patients on the pivotal trial was 31 years. Enrolled patients had received a median of 3.5 prior chemotherapy regimens. Seventy-one percent of patients were primary refractory, defined as patients who failed to achieve a complete remission to front-line chemotherapy or had relapsed within three months of receiving front-line chemotherapy. Forty-two percent of patients were refractory to their most recent prior therapy, and all patients had progressed following prior ASCT.
Seventy-five percent of patients achieved an objective response as assessed by an independent central review, including 34 percent complete remissions and 40 percent partial remissions. The median duration of response was 29 weeks by independent central review and 47 weeks by investigator assessment. Twenty-two percent of patients had stable disease, three percent had progressive disease and 1 patient was not evaluable for response. A high level of concordance was observed between independently reviewed and investigator-assessed response. Tumor reductions were achieved in 94 percent of patients. Progression-free survival (PFS) among all patients was 25 weeks by independent review and 39 weeks by investigator assessment. PFS among patients achieving a complete remission has not yet been reached. Median overall survival had not yet been reached.
The most common adverse events were peripheral sensory neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper respiratory tract infection (37 percent) and diarrhea (36 percent). The most common Grade 3 or 4 adverse events were neutropenia (20 percent), peripheral sensory neuropathy (8 percent), thrombocytopenia (8 percent) and anemia (6 percent).
The pivotal trial was conducted under a Special Protocol Assessment (SPA) with the FDA and was discussed with the EMA during the process of obtaining EU Centralized Scientific Advice on the brentuximab vedotin development program. Brentuximab vedotin has been granted orphan drug designation by the FDA and EMA for the treatment of Hodgkin lymphoma and ALCL and has been granted fast track designation by the FDA for Hodgkin lymphoma.
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, 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.
About Hodgkin 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 8,500 cases of Hodgkin lymphoma will be diagnosed in the United States during 2010 and more than 1,300 will die from the disease. 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 these patients relapse or are refractory to front-line treatment and have few therapeutic options beyond ASCT.
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 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’s lead product candidate, brentuximab vedotin, is being developed for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. 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 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 systemic 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 September 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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