Seattle Genetics Submits Supplemental BLA to FDA for Retreatment and
Extended Duration of Therapy with ADCETRIS® (Brentuximab Vedotin) in
Relapsed Hodgkin Lymphoma and Systemic ALCL
BOTHELL, Wash. -- March 18, 2013
Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that it has submitted a
supplemental Biologics License Application (sBLA) to the U.S. Food and Drug
Administration (FDA) 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).
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 sBLA submission includes data demonstrating ADCETRIS activity in managing
HL and sALCL when used in the retreatment setting, as well as beyond the 16
cycles described in our current label, while retaining a manageable safety
profile,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer
of Seattle Genetics. “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. The sBLA submission
includes data that support these uses and we look forward to the regulatory
The sBLA is based on results from a phase II 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 allowed
treatment extension and evaluated prolonged treatment with ADCETRIS beyond 16
cycles of therapy. The sBLA submission includes updated data sets from this
phase II 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.
At the 2012 ASCO Annual Meeting, retreatment data from the phase II trial were
reported from 23 patients, including one patient who was treated twice.
Patients had received a median of four prior systemic therapies, including
ADCETRIS. Of 23 evaluable patients, 70 percent (16 of 23) achieved an
objective response after retreatment with ADCETRIS, including nine complete
remissions and seven partial remissions. Median duration of retreatment
objective response was 8.8 months. Among retreated HL patients, nine of 16 (56
percent) achieved an objective response. Among retreated sALCL patients, seven
of eight (88 percent) achieved an objective response. The most common adverse
events were peripheral neuropathy (46 percent), nausea (42 percent), fatigue
(38 percent), diarrhea (33 percent) and fever (29 percent).
At the 2011 ASH Annual Meeting, prolonged 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, with
the most common adverse events being peripheral neuropathy (71 percent), upper
respiratory infection (53 percent) and fatigue (47 percent). Prolonged
treatment with ADCETRIS was associated with clinically meaningful durations of
response without worsening of toxicity over time.
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
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 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.
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 (formerly
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 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 Annual
Report on Form 10-K for the year ended December 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.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160
Tricia Larson, 425-527-4180
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