Seattle Genetics Reports Positive Data from Phase I Weekly-Dosing Clinical Trial of Brentuximab Vedotin (SGN-35) in Lymphoma

-65 percent of patients who received weekly brentuximab vedotin doses of 0.8 mg/kg and higher achieved an objective response-

SEATTLE--(BUSINESS WIRE)--Dec 7, 2009 - Seattle Genetics, Inc. (Nasdaq: SGEN) today reported data from a phase I weekly-dosing clinical trial of brentuximab vedotin (SGN-35), an antibody-drug conjugate (ADC), including multiple complete and partial remissions in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma (ALCL). The data were presented at the American Society of Hematology (ASH) 51st Annual Meeting being held in New Orleans, Louisiana.

“The encouraging data from this phase I trial in heavily pretreated lymphoma patients are consistent with the objective response rate observed in our every three week dosing phase I trial, and provide us with additional understanding about the single-agent dose, schedule and tolerability profile of brentuximab vedotin when administered weekly,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “These data reinforce our belief that brentuximab vedotin could play an important role in the treatment of Hodgkin and other CD30-positive lymphomas, and we are focused on bringing this ADC to patients as rapidly as possible. We expect data from our fully enrolled pivotal trial for relapsed and refractory Hodgkin lymphoma in the second half of 2010. If the data are supportive, we intend to use this trial as the basis for a new drug application (NDA) in the first half of 2011. We are also investigating the potential of brentuximab vedotin in other therapeutic settings, including an ongoing phase II single-agent trial for systemic ALCL and planned trials in earlier lines of therapy, such as combination regimens for Hodgkin lymphoma.”

In this single-arm trial, 44 patients were enrolled, including 38 with Hodgkin lymphoma, five with systemic ALCL and one with peripheral T-cell lymphoma. Cohorts of patients received escalating doses of brentuximab vedotin ranging from 0.4 milligrams per kilogram (mg/kg) to 1.4 mg/kg. Brentuximab vedotin was administered weekly, three out of four weeks. The median age of patients was 33 years. Enrolled patients had received a median of three prior chemotherapy regimens and 68 percent had received a prior autologous stem cell transplant. (Abstract #2731)

Key findings from the trial include:

 

  • Out of 39 patients who were evaluable for response across all dose levels, 22 (56 percent) achieved objective responses, including 13 complete remissions and nine partial remissions. Thirteen patients had stable disease and four patients had progressive disease.
  • Nineteen out of 22 responding patients remain in ongoing response. A median duration of response has not yet been met.
  • Among 31 evaluable patients treated at doses of 0.8 mg/kg and higher, 20 (65 percent) achieved an objective response, including 13 complete remissions and seven partial remissions.
  • Eighty-four percent of evaluable patients across all dose levels experienced a reduction in tumor size.
  • Among 33 patients with Hodgkin lymphoma, 17 (52 percent) achieved an objective response, including nine (27 percent) with complete remissions.
  • Among five patients with systemic ALCL, four (80 percent) achieved a complete remission.
  • Brentuximab vedotin was generally well tolerated. The majority of treatment-related adverse events were Grade 1 or 2, with the most common being peripheral neuropathy, fatigue and nausea. Grade 3 neuropathies emerged in approximately 10 percent of patients after treatment at higher weekly doses, generally beyond six months of therapy.
  • The maximum tolerated dose was identified as 1.2 mg/kg. There were few dose delays or dose eliminations.

Seattle Genetics is conducting an ongoing pivotal trial of brentuximab vedotin administered every three weeks for relapsed and refractory Hodgkin lymphoma. This trial is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA), and data are planned in the second half of 2010. In addition, the company is conducting an ongoing phase II trial for relapsed and refractory systemic anaplastic large cell lymphoma, and a phase II retreatment trial for patients who previously responded to brentuximab vedotin therapy. The company plans to initiate a phase I trial to evaluate the safety of brentuximab vedotin in combination with ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine), the standard front-line chemotherapy regimen for Hodgkin lymphoma, as well as a phase III trial for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant, both in the first half of 2010.

Brentuximab vedotin is an ADC composed of an anti-CD30 antibody attached by an enzyme-cleavable linker to a potent, synthetic antitubulin agent, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in circulation, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in targeted cell-killing.

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 pathologically 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 2009. Anaplastic large cell lymphoma is 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's lead product candidate, brentuximab vedotin, is in a pivotal trial under a special protocol assessment with the FDA. Brentuximab vedotin is empowered by Seattle Genetics' proprietary ADC technology comprising highly potent synthetic drugs and stable linkers for attaching the drugs to monoclonal antibodies. In addition, Seattle Genetics has four other product candidates in ongoing clinical trials: lintuzumab (SGN-33), dacetuzumab (SGN-40), SGN-70 and SGN-75. Dacetuzumab is being developed under a worldwide collaboration with Genentech (a wholly-owned member of the Roche Group). Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Genentech, Bayer, CuraGen, a subsidiary of Celldex Therapeutics, Progenics, Daiichi Sankyo, MedImmune, a subsidiary of AstraZeneca, and Millennium: The Takeda Oncology Company, as well as an ADC co-development agreement with Agensys, an affiliate of Astellas Pharma. 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 potential therapeutic benefit of brentuximab vedotin and plans for future 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 related to adverse clinical results as brentuximab vedotin advances in clinical trials, such as patients exhibiting progressive disease or severe adverse events; that data from the phase I clinical trials of brentuximab vedotin may not necessarily be indicative of subsequent clinical trial results, including the pivotal clinical trial results; and that the safety and/or efficacy results of these trials, including the brentuximab vedotin pivotal clinical trial for relapsed or refractory Hodgkin lymphoma, will not support an application for marketing approval in the United States or any other country. In addition, our regulatory plans may change as a result of consultation with the FDA or additional information from our clinical trials. 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, 2009 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.

 

Contact: Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160
ppinkston@seagen.com

 

Posted: December 2009

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