Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Data in
CD30-Positive Non-Hodgkin Lymphomas and Other Malignancies from Multiple
Presentations at ASH Annual Meeting
-34 Percent Objective Response Rate in Phase II Trial for Relapsed or
Refractory Non-Hodgkin Lymphomas, Including 44 Percent in Diffuse Large B-cell
-Long-term Follow-up Demonstrates Durable Complete Remissions in Pivotal
Systemic ALCL Trial-
-Investigator Data Describe CD30 Expression in up to 25 Percent of DLBCL
-Case Studies Indicate Activity of ADCETRIS in Systemic Mastocytosis-
ATLANTA -- December 09, 2012
Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS (brentuximab
vedotin) and CD30 expression data in non-Hodgkin lymphomas and other
malignancies from multiple presentations at the 54^th American Society of
Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012
in Atlanta, GA. Highlights include encouraging interim data from a phase II
clinical trial of ADCETRIS in non-Hodgkin lymphoma and long-term follow up
from a pivotal clinical trial of ADCETRIS in relapsed or refractory systemic
anaplastic large cell lymphoma (sALCL). In addition, investigators presented
data describing the expression of CD30 in DLBCL and case studies on ADCETRIS
in patients with systemic mastocytosis. ADCETRIS is an antibody-drug conjugate
(ADC) directed to CD30.
“This collection of data from both corporate studies as well as investigator
research into CD30 and the clinical role of ADCETRIS in non-Hodgkin lymphomas
add to a growing body of evidence that ADCETRIS has potential in a broad array
of CD30-positive malignancies,” said Clay B. Siegall, Ph.D., President and
Chief Executive Officer of Seattle Genetics. “The numerous data sets at ASH
also reinforce our development strategy for the program and overall vision for
ADCETRIS in the treatment of patients with significant unmet medical needs.”
A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or
Refractory CD30-Positive Non-Hodgkin Lymphomas (Abstract #2746)
In an ongoing phase II clinical trial, patients with relapsed or refractory
CD30-positive non-Hodgkin lymphomas have been enrolled, including DLBCL and
several other non-Hodgkin lymphoma subtypes. The trial is designed to assess
the antitumor activity, duration of response and safety profile of ADCETRIS in
these patients. At the time of data analysis, 73 patients had been enrolled,
including 44 with B-cell lymphoma and 29 with T-cell lymphoma. The median
number of prior systemic therapies in both lymphoma classifications was two.
Key findings include:
*Of 64 patients evaluable for response, 22 patients (34 percent) achieved
an objective response, including 12 complete remissions and ten partial
*In B-cell lymphoma subtypes, 14 of 42 evaluable patients (33 percent)
achieved an objective response, including 11 of 25 DLBCL patients (44
*In T-cell lymphoma subtypes, eight of 22 evaluable patients (36 percent)
achieved an objective response, including five of ten angioimmunoblastic
T-cell lymphoma patients (50 percent).
*The most common treatment-emergent adverse events of any grade were
fatigue (32 percent), neutropenia (26 percent), nausea (25 percent),
diarrhea (23 percent) and fever (22 percent).
*The most common Grade 3 or 4 adverse event considered related to ADCETRIS
treatment was neutropenia (28 percent). Other Grade 3 or 4 adverse events
occurring in two patients (three percent) each included anemia, decreased
appetite, hypotension and leukopenia.
*Enrollment is ongoing. For more information about this trial, visit
ADCETRIS is not approved for the treatment of the non-Hodgkin lymphoma
subtypes described in this presentation.
Long-term Remissions Observed in an Ongoing Phase II Study of Brentuximab
Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell
Lymphoma (Abstract #2745)
A pivotal, single-arm clinical trial was conducted in 58 relapsed or
refractory sALCL patients to assess efficacy and safety of single-agent
ADCETRIS. In addition, the trial was designed to determine duration of
response, progression-free survival and overall survival. Enrolled patients
had received a median of two prior chemotherapy regimens.
Data highlights from long-term patient follow up in the pivotal trial were:
*Median duration of response has not yet been reached for the 34 patients
(59 percent) who achieved a complete remission on study, and 18 patients
(53 percent) remained in continued complete remission at the time of data
*Estimated overall survival rate of patients at two years from initiation
of ADCETRIS treatment was 63 percent.
*Patients who achieved a complete remission received a median of nine doses
*The most common adverse events of any grade were peripheral neuropathy (57
percent), nausea (40 percent), fatigue (38 percent), fever (34 percent)
and diarrhea (29 percent).
*The most common Grade 3 or 4 adverse events occurring in at least five
percent of patients included Grade 3 peripheral neuropathy (17 percent),
Grade 3 neutropenia (12 percent) and Grade 4 neutropenia (9 percent).
Other Grade 3 or 4 adverse events included thrombocytopenia (14 percent)
and anemia (7 percent).
CD30 Expression in Diffuse Large B-Cell Lymphoma (Abstract #1558) and CD30
Expression in DLBCL and Its Relation to Important Clinical and Biological
Disease Features (Abstract #1592)
In two investigator-led abstracts, data described the outcome of research into
CD30 expression in DLBCL patient samples. In one presentation, data indicated
that 24.7 percent of DLBCL cases expressed CD30 by immunohistochemistry (95 of
385 samples). In a separate analysis, 23 percent of DLBCL cases expressed CD30
by immunohistochemistry (34 of 148 samples). Both investigators concluded that
clinical evaluation of ADCETRIS in DLBCL is warranted.
These findings support Seattle Genetics’ ongoing evaluation of ADCETRIS as a
treatment for DLBCL. A phase II trial for non-Hodgkin lymphoma, including
DLBCL, is currently enrolling patients.
ADCETRIS is not approved for the treatment of the DLBCL.
Anti-CD30 Antibody-Drug Conjugate Brentuximab Vedotin May Be a Promising
Treatment Option for Systemic Mastocytosis (SM) (Abstract #2857)
Systemic mastocytosis is a clonal proliferation of abnormal mast cells leading
to clinical syndromes including aggressive systemic mastocytosis (ASM) and
mast cell leukemia. ASM has been shown to express CD30. In this presentation,
data describe the outcome of two patients with ASM who had significant
clinical benefit from treatment with ADCETRIS. Both patients had a decrease in
mast cell bone marrow percentage involvement and density (including one
partial remission), as well as improved normal hematopoiesis. The investigator
noted that treatment with ADCETRIS was well-tolerated in these patients.
ADCETRIS dose level was reduced for one patient due to peripheral neuropathy
ADCETRIS is not approved for the treatment of the systemic mastocytosis.
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
ADCETRIS was granted accelerated approval by 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 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+ Hodgkin lymphoma (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
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 is 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 FDA 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
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.
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.
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 featured clinical trials and the risk of
adverse events as ADCETRIS advances in such 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.
Seattle Genetics, Inc.
Peggy Pinkston, (425) 527-4160
Tricia Larson, (425) 527-4180
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