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

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

 -Two Phase II Trials Demonstrate Greater than 65 Percent Objective Response
                     Rate in Patients with Relapsed CTCL-

       - Phase III ALCANZA Trial Ongoing to Evaluate ADCETRIS in CTCL -

54th American Society of Hematology (ASH) Annual Meeting and Exposition

Business Wire

ATLANTA -- December 10, 2012

Seattle Genetics, Inc. (Nasdaq: 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.


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

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

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

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
  *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 or

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


Seattle Genetics, Inc.
Peggy Pinkston
Tricia Larson
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