|[October 11, 2013]
Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Clinical Data in the Frontline Setting at the International Symposium on Hodgkin Lymphoma
BOTHELL, Wash. --(Business Wire)--
Genetics, Inc. (Nasdaq: SGEN) today highlighted multiple ADCETRIS
(brentuximab vedotin) data presentations at the 9th
International Symposium on Hodgkin Lymphoma (ISHL) being held October
12-15, 2013 in Cologne, Germany. ADCETRIS is an antibody-drug conjugate
(ADC (News - Alert)) directed to CD30, which is expressed in classical Hodgkin lymphoma
(HL) and systemic anaplastic large cell lymphoma (sALCL). ADCETRIS was
granted accelerated approval by the U.S. Food and Drug Administration
(FDA) in August 2011 for relapsed HL and sALCL and conditional marketing
authorization by the European Commission in October 2012 for relapsed or
refractory HL and sALCL.
"Since the last ISHL meeting in 2010, we have made significant progress
in advancing ADCETRIS, including approvals in 35 countries to date for
the treatment of relapsed HL and sALCL," said Jonathan Drachman, M.D.,
Chief Medical Officer and Executive Vice President, Research and
Development at Seattle Genetics. "In addition, we are evaluating
ADCETRIS broadly in more than 20 ongoing clinical trials, including four
global phase 3 trials in earlier lines of therapy for HL and mature
T-cell lymphoma, as well as relapsed cutaneous T-cell lymphoma. Our goal
is to establish ADCETRIS as the foundation of therapy for CD30-positive
malignancies and improve the therapeutic outcome for patients."
Three oral and nine poster presentations at ISHL illustrate the broad
clinical development program for ADCETRIS in HL, including data from a
phase 1 frontline advanced HL trial and a poster presentation describing
the ongoing global phase 3 ECHELON-1 clinical trial in frontline HL.
ADCETRIS is currently not approved for use in the treatment of newly
Frontline HL Data Presentations: Corporate-sponsored Trials
"Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD
in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma,"
(P005) by Dr. Stephen Ansell, Professor of Medicine, Division of
Hematology, Mayo Clinic
This phase 1 trial was conducted to evaluate ADCETRIS plus the
chemotherapy regimen ABVD (Adriamycin, bleomycin, vinblastine and
dacarbazine) or ADCETRIS plus AVD, which removes bleomycin, for the
treatment of newly diagnosed advanced stage HL patients.
After completing a combination regimen of ADCETRIS plus AVD, 24 of 25
patients (96 percent) achieved a complete remission. Among the patients
in the ADCETRIS plus ABVD cohorts, 21 of 22 patients (95 percent) who
completed frontline therapy on study achieved a complete remission. The
most common adverse events of any grade occurring in more than 30
percent of patients across both treatment regimens were hair loss,
constipation, diarrhea, fatigue, insomnia, nausea, neutropenia,
peripheral sensory neuropathy, fever and vomiting. As previously
reported, pulmonary toxicity was seen in the ADCETRIS plus ABVD cohorts,
resulting in a contraindication for the concomitant administration of
ADCETRIS and bleomycin. No pulmonary toxicity was observed in the
ADCETRIS plus AVD cohort.
These data support the enrollment of the ongoing global phase 3
ECHELON-1 trial. The design of the phase 3 trial will be described in a
presentation at ISHL, titled "Phase 3 Study of Brentuximab Vedotin Plus
Doxorubicin, Vinblastine and Dacarbazine (A+AVD) vs Doxorubicin,
Bleomycin, Vinblastine and Dacarbazine (ABVD) as Front-line Treatment
for Advanced Classical Hodgkin Lymphoma (HL): The ECHELON-1 Study,"
(P017) by Dr. John Radford, Professor of Medical Oncology, University of
Manchester. Visit www.clinicaltrials.org
for more information about ECHELON-1.
Frontline HL Data Presentations: Investigator-sponsored Trials
"Brentuximab Vedotin plus AVD as Initial Therapy of Non-Bulky Limited
Stage Classical Hodgkin Lymphoma: Interim Analysis of an Ongoing Phase
II Trial," (T035) by Dr. Jeremy Abramson, Director, Center for Lymphoma,
Massachusetts General Hospital
A phase 2 investigator-sponsored trial evaluating ADCETRIS plus AVD as
initial therapy for non-bulky limited stage classical HL is ongoing and
expected to evaluate this regimen in 34 patients. Under the trial
design, patients receive two cycles of single-agent ADCETRIS followed by
ADCETRIS plus AVD. In the interim analysis, 19 patients were enrolled
with a median age of 46. Of the 19 patients, 10 achieved a complete
remission after four cycles of ADCETRIS plus AVD, seven remain on
therapy and two discontinued therapy due to progressive disease or
treatment-related death. The most common adverse events of any grade
included nausea, peripheral neuropathy, fatigue, abdominal pain,
diarrhea and constipation. Grade 3 or higher adverse events included
neutropenic fever, peripheral sensory neuropathy and fatigue.
In the phase 1 corporate-sponsored study presented by Dr. Ansell at the
2013 ISHL meeting, 25 patients with advanced untreated HL were treated
with ADCETRIS in combination with AVD. Neutropenic fever was manageable
with growth factor support and peripheral neuropathy was manageable with
dose reductions or delays in the next dose of therapy. No patients who
received ADCETRIS plus AVD discontinued treatment due to adverse events.
"Sequential Brentuximab Vedotin (BV) with Adriamycin, Vinblastine,
and Dacarbazine (AVD) for Older Patients with Untreated Hodgkin
Lymphoma: Preliminary Toxicity Findings from a Phase II Window Study,"
(T077) by Dr. Andrew Evens, Chief of Hematology/Oncology, Tufts Medical
In the interim efficacy and toxicity findings of this
investigator-sponsored phase 2 trial, seven untreated, advanced stage HL
patients were enrolled with a median age of 73 and either stage II or
III disease (two patients each) or stage IV disease (three patients).
Under the trial design, older HL patients receive two cycles of
single-agent ADCETRIS followed by combination chemotherapy. In this
interim analysis, after treatment with two cycles of ADCETRIS all
patients experienced Grade 3 or higher adverse events, including
neutropenia (three patients), diarrhea (three patients), infection (two
patients) and pancreatitis (two patients). One patient death occurred
due to acute pancreatitis. Enollment of the study was temporarily
suspended but has since re-opened with monitoring of pancreatic enzymes
as well as an exclusion criterion for prior history of pancreatitis. Of
the seven patients evaluated for efficacy after receiving two doses of
ADCETRIS, one patient experienced a complete remission, four patients
experienced a partial remission and two patients experienced stable
disease. The phase 2 study is ongoing.
A corporate-sponsored retrospective analysis of patients age 60 or older
with relapsed or refractory CD30-positive hematologic malignancies
treated with ADCETRIS was presented at the American Society of
Hematology (ASH) 2012 annual meeting. The analysis assessed the efficacy
and safety of single-agent ADCETRIS among 22 sALCL patients, 16 HL
patients and two patients with other CD30-positive malignancies. Data
showed the incidence of adverse events was generally similar in older
and younger patients, with peripheral sensory neuropathy, fatigue and
anemia appearing to be more common among patients age 60 or older.
Adverse events were manageable with dose modifications or delays.
Analysis of data collected from ADCETRIS clinical trials, as well as
from the FDA Adverse Events Reporting System (FAERS) database, indicates
that the reported incidence of pancreatitis in all patients treated with
ADCETRIS is roughly one in 600. Pancreatitis is a known potential risk
factor for several products approved by the FDA for use in the lymphoma
Additional ADCETRIS Presentations:
"Progression-free Survival (PFS) Analyses of Two Pivotal Phase 2
Studies of Brentuximab Vedotin in Patients with Relapsed or Refractory
(RR) Hodgkin Lymphoma (HL) or Systemic Anaplastic Large-cell Lymphoma
(sALCL)" (P134, Corporate-sponsored Trial): Poster presentation
"PET Adapted Sequential Salvage Therapy with Brentuximab Vedotin and
Augmented ICE for Transplant Eligible Patients with Relapsed and
Refractory Hodgkin Lymphoma" (T128, Investigator-sponsored Trial):
"Phase 1/2 Study of Brentuximab Vedotin in Pediatric Patients with
Relapsed or Refractory (RR) Hodgkin Lymphoma (HL) or Systemic
Anaplastic Large-cell Lymphoma (sALCL): Interim Phase 1 Safety and
Pharmacokinetic (PK) Data" (P132, Corporate-sponsored Trial): Poster
"Post-Authorisation Safety Study (PASS) MA25101: An Observational
Cohort Study of the Safety of Brentuximab Vedotin in the Treatment of
Relapsed or Refractory (RR) CD30+ Hodgkin Lymphoma (HL) and RR
Systemic Anaplastic Large Cell Lymphoma (sALCL). The ARROVEN Study"
(P149, Corporate-sponsored Trial): Poster presentation
"Antitumor Activity of Brentuximab Vedotin in Patients with Relapsed
or Refractory (RR) Hodgkin Lymphoma (HL) Following Autologous Stem
Cell Transplant (ASCT): Meta-analysis Comparison" (P133,
Corporate-sponsored Analysis): Poster presentation
"Brentuximab Vedotin in Relapsed/Refractory (RR) Hodgkin Lymphoma (HL)
and RR Systemic Anaplastic Large-cell Lymphoma (sALCL): A Review of
International Experience in the Named Patient Program (NPP)" (P139,
Corporate-sponsored Analysis): Poster presentation
"Relapsed/Refractory (RR) Hodgkin Lymphoma (HL) Following Autologous
Stem Cell Transplant (ASCT): Burden of Illness and Advancement in
Treatment" (P144, Corporate-sponsored Analysis): Poster presentation
"UK Treatment Pathways and Resource Use Associated with
Relapsed/Refractory Hodgkin Lymphoma After Autologous Stem Cell
Transplant" (P102, Corporate-sponsored Analysis): Poster presentation
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.
ADCETRIS (brentuximab vedotin) is an antibody-drug conjugate (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 for intravenous injection 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
Seattle Genetics and Millennium: The Takeda Oncology Company, 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 Takeda 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 is also advancing a robust pipeline of
clinical-stage ADC programs: SGN (News - Alert)-75, ASG-22ME, SGN-CD19A, SGN-CD33A,
ASG-15ME and SGN-LIV1A. 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.
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
G-CSF support, 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.
Embryo-fetal toxicity: 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 therapeutic
potential of ADCETRIS. 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, but are
not limited to, risks that data resulting from the ECHELON-1 trial with
ADCETRIS will not support approvals in any of the studied indications.
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, 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.
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