Seattle
Genetics announces ADCETRIS® (Brentuximab Vedotin) Supplemental BLA accepted
for filing by the FDA. sBLA supports use of
ADCETRIS for retreatment and extended duration of therapy in relapsed Hodgkin
Lymphoma and Systemic ALCL
Full press release follows.
SOURCE: Seattle Genetics
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.
“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.”
“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 2 trial.
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
include:
Retreatment:
•
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
three-week dosing).
•
The overall objective response rate with extended treatment was
88 percent, including 76 percent complete remissions and 12 percent partial
remissions.
•
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.
About 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.
Systemic ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that also
expresses CD30.
About 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.
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.
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 lymphomas
•
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
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due
to pulmonary toxicity.
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.
Adverse Reactions:
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.
Drug Interactions:
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 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.
Contacts
Seattle Genetics, Inc.
Investors:
Peggy Pinkston, 425-527-4160
ppinkston@seagen.com
or
Media:
Tricia Larson,
425-527-4180
tlarson@seagen.com
