sBLA Supports Use of ADCETRIS for Retreatment and Extended Duration
of Therapy in Relapsed Hodgkin Lymphoma and Systemic ALCL
BOTHELL, Wash.--(BUSINESS WIRE)--May. 14, 2013--
Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that the U.S. Food
and Drug Administration (FDA) has accepted for filing a supplement to
the Biologics License Application (sBLA) supporting the use of ADCETRIS
(brentuximab vedotin) for retreatment and extended duration beyond 16
cycles of therapy in relapsed Hodgkin lymphoma (HL) and systemic
anaplastic large cell lymphoma (sALCL). The FDA is expected to take
action on the application by September 14, 2013. ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30, a defining marker of HL
and sALCL, that was granted accelerated approval by the FDA in August
2011 for relapsed HL and relapsed sALCL.
“Our goal is to broaden the ADCETRIS U.S. labeling claims to provide
both patients and physicians the opportunity to incorporate ADCETRIS
into additional HL and sALCL treatment settings,” said Clay B. Siegall,
Ph.D., President and Chief Executive Officer of Seattle Genetics. “The
FDA’s acceptance of our sBLA submission is an important step towards
making ADCETRIS available in the retreatment and extended duration
setting, and we look forward to the regulatory outcome.”
The sBLA is based on results from a phase 2 clinical trial with two
treatment arms. One arm evaluated retreatment with ADCETRIS in patients
who previously responded to treatment with ADCETRIS, then discontinued
treatment and subsequently had disease progression or relapse. The other
arm evaluated extended treatment with ADCETRIS beyond 16 cycles of
therapy. The sBLA submission includes updated data sets from this phase
Preliminary data from this trial were previously reported at the 2011
American Society of Hematology (ASH) Annual Meeting and at the 2012
American Society of Clinical Oncology (ASCO) Annual Meeting. Highlights
Of 23 evaluable patients who were retreated with ADCETRIS, 70 percent
(16 of 23) achieved an objective response, including nine complete
remissions and seven partial remissions.
Median duration of retreatment objective response was 8.8 months.
ADCETRIS was generally well tolerated in the retreatment setting. The
most common adverse events were peripheral neuropathy (46 percent),
nausea (42 percent), fatigue (38 percent), diarrhea (33 percent) and
fever (29 percent), the majority of which were Grade 1 or 2.
Extended duration of treatment:
Extended treatment data were reported from 17 patients with a median
duration of treatment of 17.3 months (approximately 24 cycles of every
The overall objective response rate with extended treatment was 88
percent, including 76 percent complete remissions and 12 percent
ADCETRIS was generally well tolerated in this setting, with the most
common adverse events being peripheral neuropathy (71 percent), upper
respiratory infection (53 percent) and fatigue (47 percent). Adverse
events were effectively managed by dose delays and reductions, with
less than ten percent of doses delayed or reduced. All events of
peripheral neuropathy and upper respiratory infection were Grade 1 and
2 and one patient experienced a Grade 3 fatigue event.
ADCETRIS is currently not approved for retreatment and extended duration
beyond 16 cycles of therapy in relapsed HL and sALCL.
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. Systemic ALCL is an aggressive type of T-cell
non-Hodgkin lymphoma that also expresses CD30.
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 was granted accelerated approval by the FDA in August 2011 and
approval with conditions by Health Canada in February 2013 for two
indications: (1) the treatment of patients with HL 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 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 sALCL. See important safety information below.
ADCETRIS is being evaluated in more than 20 ongoing clinical trials
across both corporate and investigator-sponsored studies. The trials are
designed to broadly evaluate the potential of ADCETRIS in earlier lines
of its approved indications as well as in many additional types of
CD30-positive malignancies, including cutaneous T-cell lymphoma (CTCL),
B-cell lymphomas and mature T-cell lymphomas (MTCL). For more
information, visit www.clinicaltrials.gov.
The clinical trials include:
ALCANZA, a phase 3 trial in relapsed CD30-positive CTCL
ECHELON-1, a phase 3 frontline trial in HL
ECHELON-2, a phase 3 frontline trial in MTCL
Phase 2 trial for relapsed or refractory CD30-positive non-Hodgkin
Phase 2 frontline HL in patients age 60 and older
Phase 2 trial for CD30-positive non-lymphoma malignancies
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 company’s lead program, ADCETRIS (brentuximab
vedotin), received accelerated approval from the U.S. Food and Drug
Administration in August 2011 and approval with conditions from Health
Canada in February 2013 for two indications. In addition, under a
collaboration with Millennium: The Takeda Oncology Company, ADCETRIS
received conditional approval from the European Commission in October
2012. Seattle Genetics also has four other clinical-stage ADC programs:
SGN-75, ASG-5ME, ASG-22ME and SGN-CD19A. Seattle Genetics has
collaborations for its ADC technology with a number of leading
biotechnology and pharmaceutical companies, including AbbVie, Agensys
(an affiliate of Astellas), Bayer, Celldex, 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
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 company’s
expectations for the addition of the label claims sought in the sBLA.
Factors that may cause such a difference include that the submitted data
are not sufficient to provide for approval of the claims in the sBLA.
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, 2013, 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