Seattle Genetics Submits BLA to FDA for Brentuximab Vedotin in Relapsed or Refractory Hodgkin Lymphoma and Systemic ALCL
BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that it has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the use of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of Hodgkin lymphoma and ALCL. Seattle Genetics has requested a Priority Review from the FDA that, if granted, provides six months from receipt of the submission for the FDA to take action on the application.
"This BLA submission marks a major milestone in Seattle Genetics' history and brings us one step closer to providing this important new CD30-directed ADC to Hodgkin lymphoma and ALCL patients," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "In our registration trials, nearly all patients with relapsed or refractory Hodgkin lymphoma or systemic ALCL who were treated with brentuximab vedotin had reductions in tumor volume. Importantly, a high percentage of these late-stage patients achieved an objective antitumor response with a substantial portion of durable complete remissions and a manageable safety profile. If approved, brentuximab vedotin would be the first of a new class of ADCs, representing a potentially significant step forward in the way certain types of cancer are treated."
The BLA is based on results from both a pivotal trial in relapsed or refractory Hodgkin lymphoma and a phase II trial in relapsed or refractory systemic ALCL that were presented at the 52nd American Society of Hematology (ASH) Annual Meeting in December 2010.
Results from the pivotal trial in 102 relapsed or refractory Hodgkin lymphoma patients demonstrated that:
- 94 percent of patients had reductions in tumor volume
- 75 percent of patients achieved an objective response, including 34 percent with complete remissions
- 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)
Results from the phase II trial in 58 relapsed or refractory systemic ALCL patients demonstrated that:
- 97 percent of patients had reductions in tumor volume
- 86 percent of patients achieved an objective response, including 53 percent with complete remissions
- 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 pivotal trial in Hodgkin lymphoma was conducted under a Special Protocol Assessment (SPA) with the FDA. Brentuximab vedotin has been granted orphan drug designation by the FDA 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 protease-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.
Brentuximab vedotin is in multiple ongoing trials, including a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT), 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 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 were to be diagnosed in the United States during 2010 and more than 1,300 people were expected to die from the disease. 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 Systemic ALCL
ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that highly expresses CD30. Although front-line combination chemotherapy can result in durable remissions, approximately 50 percent of ALCL patients relapse or are refractory to front-line treatment and have few therapeutic options. In the United States, approximately 2,000 systemic ALCL patients are diagnosed annually.
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 submitted a Biologics License Application for its lead product candidate, brentuximab vedotin, for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma in February 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, Pfizer 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.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the company's expectations for priority review, regulatory approval and commercial launch of brentuximab vedotin, initiation of future clinical trials and data availability from ongoing 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 that data from our clinical trials, including our pivotal Hodgkin lymphoma and phase II ALCL trial of brentuximab vedotin, will not support marketing approval for the submitted indications, or that FDA preapproval inspections of our manufacturing facilities or audits of our clinical study sites raise concerns that delay or prevent approval. In addition, we may not obtain priority review of or may have to make major amendments to our marketing application and consequently may be delayed in the planned U.S. commercial launch of brentuximab vedotin. Further, brentuximab vedotin may be approved pursuant to the accelerated approval regulations and we may be subject to completing post-marketing obligations and obtaining preapproval of our marketing and promotional materials. 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.