-Trial Conducted Under Special Protocol Assessment with FDA-
-Study Includes Evaluation of Companion Diagnostic Test for CD30
CAMBRIDGE, Mass. & BOTHELL, Wash.--(BUSINESS WIRE)--May. 7, 2012--
The Takeda Oncology Company, a wholly owned subsidiary of Takeda
Pharmaceutical Company Limited (TSE:4502) and Seattle
Genetics, Inc. (Nasdaq: SGEN), today announced the initiation of an
international pivotal phase 3 clinical trial evaluating ADCETRIS
(brentuximab vedotin) in patients with CD30-expressing cutaneous T-cell
lymphoma (CTCL) who received at least one prior systemic therapy. The
global multi-center study with ADCETRIS, an antibody-drug conjugate
(ADC) directed to CD30, will be conducted in the United States, Europe,
Australia and Brazil. The trial is being conducted under a Special
Protocol Assessment (SPA) agreement from the U.S. Food and Drug
Administration (FDA) regarding the trial design. The study also received
European Medicines Agency (EMA) scientific advice.
“Millennium is pleased to announce the initiation of the pivotal trial
of ADCETRIS in patients with relapsed CD30-expressing CTCL. We recognize
this as a significant milestone in our efforts to explore the potential
of this targeted therapy in other indications,” said Karen Ferrante, MD,
Chief Medical Officer, Millennium. “Looking forward, this study may
support the potential to supplement therapeutic options for patients,
from traditional systemic chemotherapy to ADCETRIS, a targeted therapy.”
“Data from patients with cutaneous lesions observed in our pivotal trial
in systemic anaplastic large cell lymphoma (sALCL) and interim data from
investigator-sponsored trials in CTCL with ADCETRIS provide a strong
rationale for initiating this phase 3 trial,” said Thomas C. Reynolds,
M.D., Ph.D., Chief Medical Officer, Seattle Genetics. “CTCL is an
important part of our development plan to broadly evaluate ADCETRIS in
CD30-expressing malignancies. This trial complements many other ongoing
and planned trials for patients in need, including two additional phase
3 trials for front-line Hodgkin lymphoma (HL) and front-line mature
T-cell lymphomas expected to start by late 2012 or early 2013.”
CD30 is a member of the tumor necrosis factor receptor (TNFR) family and
is a characteristic cell surface receptor for activated T-cells and
B-cells, including the malignant cells of HL and sALCL. According to
published literature, up to 50 percent of CTCL patients’ lesions express
CD30(1-3). Under a previously announced collaboration
agreement with Ventana Medical Systems, Inc. (Ventana), Millennium and
Seattle Genetics, Ventana is developing a molecular companion diagnostic
test for use in this CTCL patient population.
The study is a randomized, open-label, phase 3 trial of ADCETRIS versus
investigator’s choice of methotrexate or bexarotene in patients with
CD30-positive CTCL, including those with primary cutaneous anaplastic
large cell lymphoma (pcALCL) or mycosis fungoides (MF). The primary
endpoint of the study is overall response rate (ORR), lasting at least 4
months, with ADCETRIS in patients with CD30-positive MF or pcALCL
compared to that achieved with therapy in the control arm. The key
secondary endpoints are complete response (CR), progression-free
survival (PFS), and burden of symptoms. Approximately 124 patients will
be enrolled in the pivotal trial.
For more information about the trial, please visit www.clinicaltrials.gov.
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.
ADCETRISTM (brentuximab vedotin) received accelerated
approval from the US FDA 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
(ALCL) 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 the treatment of CTCL, front-line HL and
front-line ALCL. ADCETRIS is not approved for use outside the United
States. The marketing authorization application for ADCETRIS in relapsed
or refractory Hodgkin lymphoma and systemic ALCL, filed by Takeda Global
Research & Development Centre (Europe), was accepted for review by the
European Medicines Agency for review in June 2011.
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 Cutaneous T-Cell Lymphoma
CTCLs constitute a group of non-Hodgkin lymphomas (NHLs) and are cancers
of the T lymphocytes (a type of white blood cell) that mainly affect the
skin but can also involve the blood, lymph nodes and/or internal organs
in patients with advanced disease.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical
company based in Cambridge, Mass., markets VELCADE, a first-in-class
proteasome inhibitor, and has a robust clinical development pipeline of
product candidates. Millennium Pharmaceuticals, Inc. was acquired by
Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research,
development and commercialization activities are focused in oncology.
Additional information about Millennium is available through its
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,
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
For Seattle Genetics:
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 future
clinical trials 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-K for the year ended December
31, 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.
1. Salhany KE et al. Am J of Pathol 1988; 132(2):265-77.
2. Sigel JE et al. Mod Pathol 2000; 13(4):446–51.
3. Edinger JT et al. Am J Sur Pathol 2009; 33(12):1860-68.
Editor’s Note: This press release is also available under the Media
section of the Company’s website at: www.millennium.com/InTheNews.aspx.
Source: Millennium: The Takeda Oncology Company and Seattle Genetics, Inc.
Lindsay Treadway, 617-444-3383
Peggy Pinkston, 425-527-4160