NEW ORLEANS -- (BUSINESS WIRE) -- Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS (brentuximab vedotin) data in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma from multiple presentations at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in New Orleans, Louisiana, December 7-10, 2013. Highlights include encouraging interim data from a phase 2 clinical trial evaluating ADCETRIS as a single-agent for previously untreated HL patients age 60 or older and updated data from a phase 1 clinical trial of ADCETRIS in combination with chemotherapy for the treatment of newly diagnosed mature T-cell lymphoma (MTCL) patients, commonly referred to as peripheral T-cell lymphoma (PTCL). In addition, data were presented from an investigator-sponsored phase 2 clinical trial evaluating ADCETRIS in relapsed cutaneous T-cell lymphoma (CTCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is currently not approved for the treatment of frontline HL, frontline MTCL or relapsed CTCL.
“ADCETRIS is being evaluated broadly through more than 20 ongoing corporate and investigator-sponsored clinical trials in a variety of Hodgkin lymphoma and non-Hodgkin lymphoma disease settings,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “The interim data evaluating ADCETRIS as a treatment for older Hodgkin lymphoma patients are particularly encouraging, suggesting compelling activity and a manageable safety profile in a patient population that historically cannot tolerate conventional combination chemotherapy regimens and has inferior outcomes. In addition, updated data from trials evaluating ADCETRIS in both frontline mature T-cell lymphoma and cutaneous T-cell lymphoma provide strong rationale for the ongoing phase 3 ECHELON-2 and ALCANZA clinical trials.”
Frontline Data Presentations
A Phase 2 Study of Single-Agent Brentuximab Vedotin for Frontline Therapy of Hodgkin Lymphoma in Patients Age 60 Years and Above: Interim Results (Abstract #4389)
Data were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS as frontline therapy for patients age 60 or older with previously untreated HL. The data presented are from a trial that is designed to assess the activity and tolerability of ADCETRIS as a monotherapy for older HL patients who have received no prior treatment. Interim data were reported from 19 patients. The median age of patients was 78 years (range, 64 to 92). The data were highlighted in a poster presentation by Dr. Christopher Yasenchak from the Northwest Cancer Specialists in Tualatin, OR. The key findings included:
Brentuximab Vedotin Administered Before, During, and After Multi-agent Chemotherapy in Patients with Newly-diagnosed CD30+ Mature T- and NK-cell Lymphomas (Abstract #4386)
Data were presented from a phase 1 clinical trial evaluating ADCETRIS administered in combination with or sequentially with chemotherapy for the treatment of newly-diagnosed MTCL. Data were reported in 13 patients who received sequential treatment with two cycles of ADCETRIS followed by six cycles of the combination chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and 26 patients who received the combination regimen of ADCETRIS plus CHP (A+CHP), which removes vincristine (Oncovin). The median age of patients was 57 years. The data were highlighted in a poster presentation by Dr. Michelle Fanale from The University of Texas MD Anderson Cancer Center.
Updated key findings for ADCETRIS in combination with CHP included:
Based on these results, a global phase 3 study called ECHELON-2 was initiated and is currently enrolling patients. The ECHELON-2 trial is a randomized, double-blind, placebo-controlled, multi-center trial designed to investigate A+CHP versus CHOP as frontline therapy in patients with CD30-expressing MTCL, also known as peripheral T-cell lymphoma. Approximately 300 patients (approximately 150 patients per treatment arm) will be randomized to receive A+CHP or CHOP for six to eight cycles every three weeks.
Investigator-Sponsored Data Presentation
Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Abstract #367)
Data were presented from a phase 2 investigator-sponsored trial evaluating the use of ADCETRIS in CD30-positive CTCL patients, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). The ongoing study is being conducted by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center in Houston, TX. The primary endpoints of the trial are to evaluate the safety and activity of ADCETRIS in CD30-positive CTCL. Among 56 patients enrolled to date, 48 patients had received at least two doses of ADCETRIS and were evaluable at the time of analysis. The key findings included:
Seattle Genetics and Millennium: The Takeda Oncology Company are conducting the ALCANZA trial, a randomized phase 3 clinical trial of ADCETRIS for relapsed CD30-positive CTCL patients. The trial is assessing ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with pcALCL or MF. The primary endpoint of the study is overall response rate lasting at least four months. Approximately 124 patients will be enrolled in the pivotal trial.
ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
ADCETRIS for intravenous injection received accelerated approval from the U.S. Food and Drug Administration (FDA) and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in more than 35 countries. See important safety information below.
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS 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 biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, has been approved for two indications in more than 35 countries, including the U.S., European Union and Canada. Additionally, ADCETRIS is being evaluated broadly in more than 20 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE.
Use in Specific Populations:
MMAE exposure is increased in patients with hepatic impairment and severe renal impairment.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to our goal to establish ADCETRIS as the foundation of therapy for a broad array of CD30-positive malignancies. 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 resulting from these additional trials with ADCETRIS will not support approvals in any of the studied indications. In addition, as our other drug candidates or those of our collaborators advance in clinical trials, adverse events may occur which affect the future development of those drug candidates and possibly other compounds using similar technology, including ADCETRIS. 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, 2013 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.