|[December 09, 2013]
Seattle Genetics Highlights Data from Broad ADCETRIS® (Brentuximab Vedotin) Development Program at ASH 2013
NEW ORLEANS --(Business Wire)--
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 (News - Alert)) 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:
Of the 19 patients evaluable at the time of this analysis, 17 patients
(89 percent) had an objective response, including 12 (63 percent)
complete remissions and five (26 percent) partial remissions.
All 19 patients (100 percent) achieved tumor reduction as determined
by best percentage change from baseline.
The median duration of treatment was 18 weeks (six cycles) at the time
The most common treatment-emergent adverse events were Grade 1 or 2
and included peripheral sensory neuropathy (47 percent), fatigue (32
percent), diarrhea (26 percent), peripheral edema (26 percent),
itching (26 percent), hair loss (21 percent), nausea (21 percent) and
urinary tract infection (21 percent).
Grade 3 events occurring in one patient each included peripheral
sensory neuropathy, rash, neutropenia and dizziness upon standing. No
Grade 4 events were observed.
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:
Of 26 patients receiving the combination regimen, 23 (88 percent)
received all six cycles of initial treatment with A+CHP. Twenty-one
patients received maintenance treatment with single-agent ADCETRIS for
up to ten additional cycles.
All 26 patients (100 percent) achieved an objective response following
combination therapy, including 23 (88 percent) complete remissions and
three (12 percent) partial remissions.
All patients in complete remission after combination therapy
maintained response during maintenance. One patient with partial
remission during combination treatment converted to complete remission
The median observation time from first dose of therapy was 21.4
months. The estimated one-year progression-free survival rate was 71
percent and one-year overall survival rate was 88 percent.
The most common treatment-emergent adverse events of any grade
occurring in more than 40 percent of patients were peripheral sensory
neuropathy (69 percent), nausea (65 percent), diarrhea (58 percent),
fatigue (58 percent), shortness of breath (46 percent) and
constipation (38 percent).
The most common Grade 3 treatment-emergent adverse events were febrile
neutropenia, anemia and peripheral sensory neuropathy.
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 (News - Alert)-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:
Thirty-five of 48 patients (73 percent) achieved an objective
response, including 20 of 20 (100 percent) with LyP and/or pcALCL and
15 of 28 (54 percent) with MF.
In patients with MF, the median time to response was 12 weeks and the
median duration of response was 32 weeks. In patients with LyP and/or
pcALCL, the median time to response was three weeks and the median
duration of response was 26 weeks.
Responses were observed in patients with CD30 expression levels
ranging from less than 10 percent to more than 50 percent based on
standard screening methods.
The most common adverse events were peripheral neuropathy (65
percent), fatigue (41 percent) and rash (27 percent). Other common
adverse events included nausea, neutropenia, myalgia, diarrhea and
localized skin infection.
The most common Grade 3 adverse events were neutropenia (five three
patients), nausea (two patients), chest pain (two patients),
arthralgia (two patients) and infection (two patients). Other Grade 3
or 4 events occurring in one patient each included fatigue, deep vein
thrombosis, elevated liver function tests and dehydration. Two patient
deaths occurred due to untreated sepsis, including one elderly patient
with ALCL after one dose and one patient due to a urinary tract
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 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
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