Seattle Genetics Highlights Multiple ADCETRIS® (Brentuximab Vedotin) Data Presentations in Frontline and Salvage Hodgkin Lymphoma at ASH Annual Meeting

SAN FRANCISCO, CA, USA I December 8, 2014 I Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted multiple ADCETRIS (brentuximab vedotin) data presentations in frontline and salvage Hodgkin lymphoma (HL) at the 56^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA, December 6-9, 2014. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL), a type of T-cell lymphoma. Data highlighted in oral sessions include encouraging long-term outcomes from a phase 1 trial evaluating ADCETRIS in combination with AVD chemotherapy in frontline HL, as well as strong activity evaluating ADCETRIS combination therapy in second-line HL and ADCETRIS monotherapy or combination therapy in frontline HL patients age 60 and older. In addition, encouraging data from multiple investigator-sponsored trials were featured in oral and poster sessions evaluating ADCETRIS in frontline and salvage HL and in non-Hodgkin lymphoma settings.

“Our goal is to establish ADCETRIS as the foundation of therapy for CD30-positive malignancies. The multiple data sets presented at the ASH annual meeting support that vision, showing encouraging activity associated with ADCETRIS treatment both as a single-agent and in combination with other agents for frontline and salvage Hodgkin lymphoma,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Of note, the oral presentation on the three-year long term follow-up from the phase 1 frontline Hodgkin lymphoma trial, demonstrating a failure-free survival rate of 92 percent and overall survival rate of 100 percent with a manageable safety profile, supports our goal to redefine frontline treatment of Hodgkin lymphoma with the addition of ADCETRIS. The phase 3 ECHELON-1 trial is evaluating ADCETRIS in this setting.”

Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long-Term Outcomes (Abstract #292, oral presentation at 7:45 a.m. PT at the Moscone Center, West Building, 3009-3011-3022-3024)

This phase 1 trial was conducted to evaluate ADCETRIS plus the chemotherapy regimen ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or ADCETRIS plus AVD, which removes bleomycin, for the treatment of newly diagnosed advanced stage HL patients.

Data previously presented from this trial demonstrated that 24 of 25 patients (96 percent) who received ADCETRIS plus AVD achieved a complete remission and 21 of 22 patients (95 percent) who completed therapy with ADCETRIS plus ABVD achieved a complete remission. The most common adverse events of any grade occurring in more than 30 percent of patients across both treatment regimens were hair loss, constipation, diarrhea, fatigue, insomnia, nausea, neutropenia, peripheral sensory neuropathy, fever and vomiting. As previously reported, pulmonary toxicity was seen in the ADCETRIS plus ABVD cohorts, resulting in a contraindication for the concomitant administration of ADCETRIS and bleomycin. No pulmonary toxicity was observed in the ADCETRIS plus AVD cohort.

Long-term data to be presented in an oral presentation by Joseph Connors, M.D., BC Cancer Agency, include:

• In the ADCETRIS plus AVD arm, three-year overall survival was 100 percent and three-year failure-free survival was 92 percent. In the ADCETRIS plus ABVD arm, three-year overall survival was 92 percent and three-year failure-free survival was 79 percent.
• Patients were followed for a median of 36 months in the ADCETRIS plus AVD arm and 45 months in the ADCETRIS plus ABVD arm. The longest time to relapse in either arm was 23 months.

Based on the phase 1 results, the global phase 3 ECHELON-1 trial was initiated and is currently enrolling patients. This randomized trial is comparing progression-free survival in patients receiving ADCETRIS in combination with AVD to patients receiving ABVD alone. Visit www.clinicaltrials.org for more information about ECHELON-1.

Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory to Frontline Therapy (Abstract #293, oral presentation at 8:00 a.m. PT at the Moscone Center, West Building, 3009-3011-3022-3024)

Interim data were presented from an ongoing phase 1/2 single-arm, open-label clinical trial evaluating the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients who have relapsed or were refractory to frontline therapy. Current treatment options in this setting include salvage chemotherapy regimens that historically have resulted in variable complete remission rates of 19 to 60 percent and are associated with significant toxicities.

The phase 1 study determined the dosing level of bendamustine combined with ADCETRIS, and assessed safety and tolerability. The phase 2 expansion cohort is evaluating combination treatment of ADCETRIS and bendamustine to assess best response, duration of response and progression-free survival. In the trial, ADCETRIS in combination with bendamustine is administered every three weeks, for up to six cycles, followed by additional treatment with single-agent ADCETRIS for up to a total of 16 cycles of therapy. After patients receive at least two cycles of combination therapy, they have the option to pause treatment to receive an autologous stem cell transplant (ASCT) and then resume treatment with single-agent ADCETRIS as consolidation.

Data were reported from 54 patients with a median age of 37 years. The majority of patients (54 percent) had stage III/IV disease at the time of initial diagnosis and 37 patients (69 percent) had either primary refractory disease or had relapsed within one year of frontline therapy. Interim data from this phase 1/2 trial to be highlighted in an oral presentation by Ann LaCasce, M.D., Dana-Farber Cancer Institute, include:

• Of 48 patients evaluable for response, 46 patients (96 percent) had an objective response, including 40 patients (83 percent) with a complete remission and six patients (13 percent) with a partial remission. One patient had stable disease and one patient had progressive disease. The majority of complete remissions (34 of 40 patients) were achieved after two cycles of combination therapy.
• Median duration of response, progression-free survival and overall survival had not yet been reached.
• No adverse impact on stem cell mobilization or engraftment was observed. Thirty-two patients had received an ASCT to date.
• The most common adverse events from combination treatment were infusion-related reactions (IRRs) which were seen in approximately 50 percent of patients. Approximately 20 percent of IRRs were Grade 3 or higher. The majority of IRRs occurred within 24 hours of the second cycle of combination treatment and were considered related to both therapies. Symptoms associated with IRRs were dyspnea (15 percent), chills (13 percent) and flushing (13 percent). The trial protocol was amended to require premedication with corticosteroids and antihistamines, which decreased the severity of IRRs.

Brentuximab Vedotin Monotherapy and in Combination with Dacarbazine in Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Phase 2 Study (Abstract #294, oral presentation at 8:15 a.m. PT at the Moscone Center, West Building, 3009-3011-3022-3024)

Data were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS as a single-agent or in combination with dacarbazine as frontline therapy for HL patients age 60 or older. Interim data were reported from 27 patients treated with single-agent ADCETRIS and 18 patients treated with the combination of ADCETRIS and dacarbazine. The median age of patients was 78 years in the single-agent ADCETRIS arm and 72.5 years in the dacarbazine combination arm. A majority of patients in each arm had stage III/IV disease at the time of diagnosis. The data will be highlighted in an oral presentation by Andres Forero-Torres, M.D., University of Alabama at Birmingham.

Data from the single-agent ADCETRIS arm include:

• Of 27 evaluable patients, 25 patients (93 percent) had an objective response, including 19 patients (70 percent) with a complete remission and six patients (22 percent) with a partial remission. Two patients (seven percent) had stable disease.
• All 27 patients (100 percent) achieved tumor reduction.
• After a median follow-up time of 8.7 months, the median duration of response was 9.1 months and the median PFS was 10.5 months.
• The median number of treatment cycles was eight.
• The most common adverse events of any grade occurring in 20 percent or more of patients were peripheral sensory neuropathy, fatigue, nausea, swelling, diarrhea, decreased appetite and constipation.
• The only Grade 3 adverse events occurring in more than one patient were peripheral sensory neuropathy (seven patients) and peripheral motor neuropathy and rash (two patients each). No Grade 4 adverse events occurred.

Preliminary key findings in the ongoing trial evaluating combination ADCETRIS and dacarbazine include:

• Of 14 evaluable patients, 13 patients (93 percent) had an objective response, including four patients (29 percent) with a complete remission and nine patients (64 percent) with a partial remission.
• All 14 evaluable patients (100 percent) achieved tumor reduction.
• Fifteen of 18 patients (83 percent) were still on treatment at the time of the analysis.
• The most common Grade 1 and 2 adverse events were peripheral sensory neuropathy and nausea (33 percent each); diarrhea and constipation (28 percent each); fatigue, hair loss, joint pain and headache (22 percent each).
• Grade 3 or serious adverse events occurring in one patient each were colitis and vomiting, hypotension and hyperglycemia.
• The trial is currently enrolling patients to evaluate the combination of ADCETRIS and bendamustine.

Additional ADCETRIS Data Presentations

Additional investigator-sponsored data presentations evaluating ADCETRIS in Hodgkin and non-Hodgkin lymphoma include:

• Cost-Effectiveness Assessment of Brentuximab Vedotin to Prevent Progression Following Autologous Stem Cell Transplant in Hodgkin Lymphoma in the United States (Abstract #2657, poster presentation by Joshua Roth, Ph.D., M.H.A., Fred Hutchinson Cancer Research Center, at 6:00 p.m. PT on Sunday, December 7, 2014 at the Moscone Center North Building, Hall E )
• Brentuximab Vedotin (BV) Plus Rituximab (R) as Frontline Therapy for Patients (Pts) with Epstein Barr Virus (EBV)+ and/or CD30+ Lymphoma: Phase I Results of an Ongoing Phase I-II (Abstract #3096, poster presentation by Mitul Gandhi, M.D., Northwestern University Feinberg School of Medicine, at 6:00 p.m. PT on Sunday, December 7, 2014)
• Safety and Early Efficacy in an Ongoing Pilot Study of Brentuximab Vedotin and AVD Chemotherapy Followed By 30 Gray Involved-Site Radiotherapy for Newly Diagnosed, Early Stage, Unfavorable Risk Hodgkin Lymphoma (Abstract #3085, poster presentation on Monday, December 8, 2014)
• A Phase 1-2 Study of Brentuximab Vedotin (BV) and Bendamustine (B) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) and Anaplastic Large T-Cell Lymphoma (ALCL) (Abstract #3084, poster presentation on Monday, December 8, 2014)
• Results of a Phase II Trial of Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT (Abstract #501, oral presentation at 3:15 p.m. PT on Monday, December 8, 2014)
• A Phase 2 Trial of Induction Chemotherapy with ABVD Followed by Brentuximab Vedotin Consolidation in Patients with Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma (Abstract #4431, poster presentation on Monday, December 8, 2014)
• Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides or Sézary Syndrome: Final Results Show Significant Clinical Activity and Suggest Correlation with CD30 Expression (Abstract #804, oral presentation at 8:45 a.m. PT on Tuesday, December 9, 2014)

ADCETRIS is currently not approved in the frontline, salvage or combination Hodgkin and non-Hodgkin lymphoma settings or in cutaneous T-cell lymphoma.

About ADCETRIS

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 and release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection received accelerated approval from the U.S. Food and Drug Administration and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of 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 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 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 45 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda 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, is commercially available for two indications in more than 45 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, 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.

SOURCE: Seattle Genetics