Seattle Genetics and Millennium Report Positive Data from Phase II Trial of Brentuximab Vedotin (SGN-35) in Relapsed or Refractory ALCL at ASH Annual Meeting
-97 Percent of Patients Had Reductions in Tumor Volume-
-53 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., Dec 07, 2010 (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 data from a phase II clinical trial of single-agent brentuximab vedotin (SGN-35) in relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Brentuximab vedotin is an antibody-drug conjugate (ADC) targeted to CD30, a defining marker of ALCL. The data were presented today during an oral session at the 52nd American Society of Hematology (ASH) Annual Meeting in Orlando, FL.
Key findings from the trial in 58 relapsed or refractory ALCL patients included:
- 86 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.
- 53 percent of patients achieved a complete remission.
- The median duration of response by independent assessment had not yet been reached at a median follow up on study of six months.
- Tumor reductions were achieved in 97 percent of patients.
- Brentuximab vedotin treatment was associated with manageable adverse events, with the most common being nausea, peripheral sensory neuropathy, fatigue, fever and diarrhea. The most common Grade 3 or higher adverse events were neutropenia, peripheral sensory neuropathy, thrombocytopenia and anemia.
"Nearly all patients in this trial had reductions in tumor volume, including a remarkable rate of complete remissions," said Dr. Andrei Shustov, assistant professor of Hematology at the University of Washington School of Medicine and attending physician in the Hematologic Malignancies Program at the Seattle Cancer Care Alliance. "This suggests that brentuximab vedotin has the potential to provide a promising new treatment option for patients with relapsed or refractory systemic ALCL. The data are also supportive of continued clinical evaluation of brentuximab vedotin in earlier lines of ALCL treatment, and in other CD30-positive malignancies."
"Single-agent activity of this magnitude is rarely seen in oncology. It is particularly impressive when demonstrated in a pretreated disease population," said Dr. Pier Zinzani, Associate Professor, Institute of Hematology "Seràgnoli" University of Bologna, Italy. "There have been no major treatment advances in relapsed or refractory ALCL in many years. We are excited by the potential of adding brentuximab vedotin to the armamentarium of treatment options."
Seattle Genetics plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2011, and seek approval for both relapsed or refractory Hodgkin lymphoma and relapsed or refractory systemic ALCL. Millennium has initiated discussions with European regulators to support the submission of a Marketing Authorization Application 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 Phase II Trial Design (Abstract #961)
The single-arm trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory systemic ALCL 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 overall 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 of the trial included complete response rate, duration of response, progression-free survival, overall survival and tolerability. Brentuximab vedotin has been granted orphan drug designation by the FDA and European Medicines Agency (EMA) for the treatment of Hodgkin lymphoma and ALCL.
The median age of patients in the phase II trial was 52 years. Enrolled patients had received a median of two prior chemotherapy regimens. Sixty-two percent of patients were primary refractory, defined as patients who did not achieve a complete remission to front-line chemotherapy or who relapsed within three months of receiving front-line chemotherapy. Seventy-two percent of patients were anaplastic lymphoma kinase (ALK) negative, generally suggesting a poor prognosis. Twenty-four percent of patients did not respond to any prior treatment, and 26 percent had failed prior autologous stem cell transplant.
Eighty-six percent of patients achieved an objective response as assessed by an independent central review, including 53 percent complete remissions and 33 percent partial remissions. An additional three percent of patients had stable disease, five percent had progressive disease and five percent were not evaluable or were histologically ineligible. A high level of concordance was observed between independently reviewed and investigator-assessed response. Median duration of response and median progression-free survival had not yet been reached. Tumor reductions were achieved in 97 percent of patients. B-symptoms resolved in 82 percent of patients in whom such symptoms were present at baseline (14 out of 17). Thirty-one percent of patients remained on treatment.
The most common adverse events were nausea (38 percent), peripheral sensory neuropathy (38 percent), fatigue (34 percent), fever (33 percent) and diarrhea (29 percent). The most common Grade 3 adverse events were neutropenia (21 percent), thrombocytopenia (14 percent), peripheral sensory neuropathy (10 percent) and anemia (7 percent).
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 Systemic 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. ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that highly expresses CD30.
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 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.