-Interim Data Demonstrate 75 Percent Response Rate in Patients with
BOTHELL, Wash.--(BUSINESS WIRE)--May. 10, 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 relapsed cutaneous
T-cell lymphoma (CTCL) were presented at the Society for Investigative
Dermatology annual meeting being held May 9-12, 2012 in Raleigh, NC.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS
has not been approved for use in CTCL.
The trial enrolled CTCL patients with mycosis fungoides (MF) or Sezary
syndrome. At the time of data analysis, 17 patients had been enrolled,
including 16 with MF and one with Sezary syndrome. Patients had received
a median of six prior therapies, including a median of four 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,
progression-free survival and safety. The study is led by principal
investigator Dr. Youn H. Kim, Professor, Department of Dermatology, and
Director, Multidisciplinary Cutaneous Lymphoma Program at Stanford
University School of Medicine in Stanford, CA. Key findings include:
Twelve of 16 evaluable patients (75 percent) achieved a partial
remission. Three patients had stable disease and one patient had
progressive disease. One patient was not yet evaluable for response.
Median CD30 expression on lymphoid cells in biopsies of skin lesions
was 15 percent. Clinical activity was not dependent on CD30 expression
Sixty-eight percent of patients maintained response at week 25. Median
duration of response had not yet been reached.
Adverse events were mostly Grade 1 or 2, with the most common related
events being peripheral neuropathy (76 percent), fatigue (65 percent),
decreased appetite (30 percent) and generalized skin eruption (30
percent). The most common event of Grade 3 or higher was generalized
skin eruption (18 percent). One patient experienced Grade 4 peripheral
neuropathy. There was one patient death due to respiratory failure
presumably secondary to pneumonia.
This is the second data set reported with ADCETRIS in CTCL patients. At
the T-Cell Lymphoma Forum in January 2012, interim data were presented
from a phase II investigator-sponsored trial in CD30-positive CTCL
patients, including lymphomatoid papulosis, primary cutaneous anaplastic
large cell lymphoma (pcALCL) or MF. In the trial, which is being
conducted by Dr. Madeleine Duvic at The University of Texas MD Anderson
Cancer Center, 11 of 17 evaluable patients (65 percent) achieved an
objective response, including seven complete remissions (CRs) and four
partial remissions (PRs). The most common adverse events were Grade 1,
including diarrhea, chest tightness, alopecia, nausea, elevated liver
enzymes and peripheral neuropathy.
Seattle Genetics and Millennium: The Takeda Oncology Company recently
initiated a randomized phase III clinical trial of ADCETRIS for relapsed
CD30-positive CTCL patients. The trial will assess 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 4
months. Approximately 124 patients will be enrolled in the pivotal
trial. The phase III 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.
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
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 (brentuximab vedotin) received accelerated approval from the
U.S. Food and Drug Administration 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 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 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, 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 March 31, 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.
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160