Millennium and Seattle Genetics Initiate Global Phase 3 Clinical Trial of
ADCETRIS® in Previously Untreated Advanced Hodgkin Lymphoma
− First randomized clinical trial designed to examine the use of ADCETRIS as
part of a frontline treatment regimen for patients with previously untreated
classical Hodgkin lymphoma −
CAMBRIDGE, Mass. & BOTHELL, Wash. -- November 01, 2012
Millennium: 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 phase 3 clinical
trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline
combination chemotherapy regimen in patients with previously untreated
advanced Hodgkin lymphoma (HL). The trial is being conducted under a Special
Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration
(FDA) and the trial also received scientific advice from the European
Medicines Agency (EMA). ADCETRIS is an antibody-drug conjugate (ADC) directed
to CD30, a defining marker of classical HL.
“Millennium is pleased to announce the initiation of the phase 3 trial of
ADCETRIS in patients with previously untreated advanced Hodgkin lymphoma. This
is a key step in our efforts to explore the potential of this targeted therapy
as part of a frontline treatment regimen,” said Karen Ferrante, MD, Chief
Medical Officer, Millennium.“The trial is part of our ongoing development
program to explore patient populations that may benefit from treatment with
ADCETRIS in earlier lines of therapy and in other CD30-expressing
“There have been no new therapies approved for patients with newly diagnosed
HL in many decades, representing a significant need to identify additional
treatment options in this setting,” said Thomas C. Reynolds, M.D., Ph.D.,
Chief Medical Officer, Seattle Genetics. “We believe through this novel
ADCETRIS-containing regimen we have the potential to redefine the treatment of
frontline HL. This trial is also an important part of our development plan for
ADCETRIS, and may serve as confirmatory to our U.S. accelerated approval in
relapsed HL and systemic anaplastic large cell lymphoma.”
The randomized, open-label, phase 3 trial will investigate ADCETRIS+AVD^1
versus ABVD^2 as frontline therapy in patients with advanced classical HL. The
primary endpoint is modified progression free survival (mPFS) per independent
review facility assessment using the Revised Response Criteria for malignant
lymphoma. Secondary endpoints include overall survival (OS), complete
remission (CR) and safety. The multi-center trial will be conducted in North
America, Europe, Latin America and Asia. The study will enroll approximately
1,040 eligible patients (approximately 520 patients per treatment arm) who
have histologically-confirmed diagnosis of Stage III or IV classical HL who
have not been previously treated with systemic chemotherapy or radiotherapy.
For more information, 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
ADCETRIS received accelerated approval from 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 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
See important safety information below.
ADCETRIS is not approved for use outside the United States. The Marketing
Authorization Application (MAA) for ADCETRIS in relapsed or refractory Hodgkin
lymphoma and sALCL, filed by Takeda Global Research & Development Centre
(Europe), Ltd., was accepted for review by the European Medicines Agency (EMA)
in June 2011. In July 2012, the Committee for Medicinal Products for Human Use
(CHMP) of the EMA issued a positive opinion for the conditional marketing
authorization of brentuximab vedotin for two indications.
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 Hodgkin Lymphoma
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. Hodgkin lymphoma is distinguished from other types
of lymphoma by the presence of one characteristic type of cell, known as the
Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30.
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 website,
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, 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 phase III trial 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-Q for the quarter ended June 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
^1 Adriamycin, vinblastine, dacarbazine
^2 Adriamycin, bleomycin, vinblastine, dacarbazine
Lindsay Treadway, +1-617-444-3383
Peggy Pinkston, +1-425-527-4160
Tricia Larson, +1-425-527-4180
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