Seattle Genetics Announces Data from Investigator-Sponsored Trials of ADCETRIS® (Brentuximab Vedotin) in Cutaneous T-Cell Lymphoma at ASH Annual Meeting

ATLANTA--(BUSINESS WIRE)--

Seattle Genetics, Inc. SGEN today announced that results from two ongoing investigator-sponsored phase II clinical trials of ADCETRIS (brentuximab vedotin) in patients with relapsed cutaneous T-cell lymphoma (CTCL) were presented at the 54^th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS has not been approved for use in the treatment of CTCL.

Brentuximab Vedotin Demonstrates Significant Clinical Activity in Relapsed or Refractory Mycosis Fungoides with Variable CD30 Expression (Abstract #797)

The ongoing phase II clinical trial is enrolling CTCL patients with mycosis fungoides (MF) or Sezary syndrome. Twenty patients have been enrolled to date with a median of six prior systemic therapies. The primary endpoint of the trial is clinical response rate. Secondary endpoints include correlation of clinical response with CD30 expression levels, duration of response and safety. The study was led by principle investigator Dr. Youn H. Kim from Stanford University School of Medicine in Stanford, CA, and was presented in an oral session. Key findings include:

• Fourteen of 20 patients (70 percent) achieved an objective response across all stages of disease, including Stage IB, Stage IIB and Stage IVA/B. At the time of analysis, 14 patients had a partial response, one patient had stable disease and four patients had progressive disease. One patient was not evaluable for response.
• CD30 expression on lymphoid cells in biopsies of skin lesions was measured by immunohistochemistry (IHC) and patients were divided into three groups: those with less than 10 percent expression (seven patients), 10 percent to 50 percent expression (10 patients) and greater than 50 percent expression (three patients). Clinical activity was observed in all three groups.
• The most common related adverse events of any grade were peripheral neuropathy (70 percent), fatigue (60 percent), decreased appetite (30 percent) and nausea (25 percent).
• The most common Grade 3 or 4 related adverse events were rash (three patients) and neutropenia (two patients).

Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Abstract #3688)

Data were presented from a phase II 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 MF. The ongoing study is being conducted by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center in Houston, TX. Among 54 patients enrolled to date, 46 patients were evaluable at the time of analysis. The primary endpoint of the trial is to evaluate the safety and efficacy of ADCETRIS in CD30-positive CTCL. The key findings include:

• Thirty-one of 46 patients (67 percent) achieved an objective response, including 19 of 19 (100 percent) with LyP and/or pcALCL and 12 of 27 (44 percent) with MF.
• The most common adverse events were peripheral neuropathy (44 percent), fatigue (30 percent), skin rash (26 percent), diarrhea (22 percent), nausea (18 percent) and myalgia (18 percent).
• The most common Grade 3 adverse events were neutropenia (three patients), elevated liver function tests (two patients), nausea (two patients) and deep vein thrombosis (two patients).

Seattle Genetics and Millennium: The Takeda Oncology Company have initiated the ALCANZA trial, a randomized phase III 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. The ALCANZA trial is being conducted under a Special Protocol Assessment agreement from the U.S. Food and Drug Administration (FDA). The study also received European Medicines Agency scientific advice.

About CTCL

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. Cutaneous lymphomas are a category of non-Hodgkin lymphomas that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, up to 50 percent of CTCL patients' lesions express CD30.

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 but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) the treatment of patients with Hodgkin lymphoma 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 the treatment of adult patients with relapsed or refractory CD30+ HL: (1) following autologous stem cell transplant (ASCT), or (2) following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). 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 monoclonal antibody-based therapies for the treatment of cancer. The U.S. Food and Drug Administration granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys and Genmab. More information can be found at www.seattlegenetics.com.

U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.

Contraindication:

Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.

Warnings and Precautions:

• Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
• Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
• Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
• Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
• Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
• Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.

Adverse Reactions:

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.

Drug Interactions:

Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.

For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS and initiation of 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 the inability to show sufficient activity in the phase III trial and the risk of adverse events as ADCETRIS advances in clinical trials. In addition, data from our clinical trials, including our pivotal trials which were the basis for FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. 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, 2012 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.