-Interim Data Demonstrate 65 Percent Response Rate in Patients with
-Two Case Studies Provide First Report of Activity and Tolerability
in PTCL-NOS Patients-
SAN FRANCISCO--(BUSINESS WIRE)--Jan. 26, 2012--
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that interim
results from an investigator-sponsored phase II clinical trial of
ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell
lymphoma (CTCL) were presented at the T-Cell Lymphoma Forum being held
January 26-28, 2012 in San Francisco, CA. In addition, case studies were
presented on two patients with relapsed peripheral T-cell lymphoma-not
otherwise specified (PTCL-NOS) who were treated with ADCETRIS. ADCETRIS
is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is not
approved for use in CTCL or PTCL-NOS.
Investigator-Sponsored Phase II Trial in CTCL
At the time of data analysis, 17 of 23 enrolled patients had received at
least two doses of ADCETRIS and were evaluable for response. All
patients had relapsed CD30-positive cutaneous lymphoproliferative
disorders, including lymphomatoid papulosis (LyP), primary cutaneous
anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF).
Patients treated in this trial receive 1.8 milligrams per kilogram
(mg/kg) of ADCETRIS every three weeks for up to a maximum of eight
doses. Patients who achieve partial remission or stable disease are
eligible to receive an additional eight doses. Key findings, which were
presented by Dr. Madeleine Duvic from The University of Texas MD
Anderson Cancer Center, include:
Eleven of 17 evaluable patients (65 percent) achieved an objective
response, including seven complete remissions (CRs) and four partial
remissions (PRs). Six patients had stable disease. These
investigator-assessed responses were observed in all three subtypes of
The most common adverse events were Grade 1, including diarrhea, chest
tightness, alopecia, nausea, elevated liver enzymes and peripheral
neuropathy. ADCETRIS treatment was held in two patients with Grade 2
peripheral sensory neuropathy and in one patient with Grade 4
neutropenia and Grade 3 leukopenia. One patient died of sepsis after
one dose of ADCETRIS.
Variable CD30 expression was observed in baseline lesions.
The clinical trial is ongoing with planned enrollment of 29 patients.
PTCL Case Studies
Data were also presented from case studies of two patients with relapsed
CD30-positive PTCL-NOS who were enrolled in phase I trials of ADCETRIS.
PTCL-NOS is associated with a poor prognosis and there is no
well-established standard of care. Both patients were heavily
pretreated, including prior autologous stem cell transplant. The first
patient achieved a PR with progression-free survival of eight months and
overall survival of 22 months. Adverse events considered related to
ADCETRIS were Grade 2 sensory neuropathy in the fingertips and Grade 3
fatigue. The second patient achieved a CR which is still ongoing with a
duration of more than 19 months. The patient had Grade 3 anemia and
other Grade 1 adverse events, none of which were considered by the
investigator to be related to 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.
Seattle Genetics and Millennium: The Takeda Oncology Company 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.
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 has not been approved for use in CTCL or PTCL-NOS.
ADCETRIS is not approved for use outside the United States. The
marketing authorization application for ADCETRIS in relapsed or
refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research &
Development Centre (Europe), was accepted by the European Medicines
Agency for review in June 2011.
Seattle Genetics and Millennium: The Takeda Oncology Company are
planning a phase III clinical trial of ADCETRIS in CD30-positive CTCL
patients to begin by mid-2012.
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 that 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.
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, Bayer, Celldex Therapeutics, Daiichi
Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as
well as ADC co-development agreements with Agensys, an affiliate of
Astellas, 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
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.
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
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
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, 2011 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.
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160