Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Data in Relapsed
Hodgkin Lymphoma and Other CD30-Positive Malignancies from Multiple
Presentations at ASH Annual Meeting
-Long-Term Follow-up from ADCETRIS Pivotal HL Trial Demonstrates an Estimated
Two Year Survival Rate of 65 Percent-
-Investigator Analysis Shows Median Overall Survival for ADCETRIS-Treated
Relapsed HL Patients after ASCT Was 91 Months Compared with 28 Months among
-ADCETRIS Activity and Tolerability Observed in the Treatment of Salvage HL
and Patients Age 60 and Over with CD30-Positive Hematologic Malignancies-
ATLANTA -- December 10, 2012
Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS (brentuximab
vedotin) data in relapsed Hodgkin lymphoma (HL) and other CD30-positive
malignancies from multiple presentations at the 54^th American Society of
Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012
in Atlanta, GA. Highlights include compelling survival data from long-term
follow up in a pivotal clinical trial of ADCETRIS in relapsed or refractory HL
and a retrospective comparison of overall survival among patients treated with
ADCETRIS to those not treated with ADCETRIS following an autologous stem cell
transplant (ASCT). In addition, data describe the activity and tolerability of
ADCETRIS in the salvage HL setting from an investigator-sponsored trial and in
relapsed patients age 60 or over with CD30-positive malignancies, including
HL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining
marker of classical HL.
"There are more than a dozen data presentations at ASH evaluating the use of
ADCETRIS in CD30-positive malignancies and we are very encouraged by both the
broad application across multiple hematologic disease areas as well as the
encouraging activity associated with ADCETRIS,” said Clay B. Siegall, Ph.D.,
President and Chief Executive Officer of Seattle Genetics. “The extensive
investigator and corporate data presentations at ASH clearly demonstrate the
important role ADCETRIS plays in the treatment of relapsed HL and systemic
anaplastic large cell lymphoma and the promise of the role it potentially will
play in additional future indications.”
Long-term Survival Analysis of an Ongoing Phase 2 Study of Brentuximab Vedotin
in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #3689)
A pivotal, single-arm trial was conducted in 102 relapsed or refractory HL
patients after ASCT to assess efficacy and safety of single-agent ADCETRIS. In
addition, the trial was designed to determine duration of response,
progression-free survival and overall survival. Enrolled patients had received
a median of more than three prior chemotherapy regimens.
Data highlights from the long-term survival analysis in the pivotal trial
*After a median observation time of approximately 2.5 years from first dose
of ADCETRIS, 59 percent of patients (60 of 102 patients) were alive and
the median overall survival had not yet been reached.
*The estimated two year survival rate was 65 percent, including 91 percent
for patients who achieved a complete remission.
*Improved overall survival and progression-free survival correlated with
PET (positron emission tomography) evaluation at Cycle four.
*There was no significant difference in prolonged overall survival in
patients whose disease progressed less than or more than one year
following ASCT. The only pretreatment factor that was associated with a
higher two year survival rate was a baseline ECOG score of 0.
*The most common adverse events of any grade were peripheral sensory
neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper
respiratory tract infection (37 percent) and diarrhea (36 percent).
*Among the most common adverse events of any grade, the most common Grade 3
or 4 adverse events were neutropenia (14 percent Grade 3, 6 percent Grade
4) and peripheral sensory neuropathy (9 percent Grade 3). Other Grade 3 or
4 adverse events occurring in at least five percent of patients were
thrombocytopenia (8 percent) and anemia (6 percent).
Overall Survival Benefit for Patients with Relapsed Hodgkin Lymphoma Treated
with Brentuximab Vedotin After Autologous Stem Cell Transplant (Abstract
An independent retrospective comparison conducted by MD Anderson Cancer Center
evaluated overall survival in 102 relapsed HL patients treated with ADCETRIS
in a pivotal clinical trial compared to data from 756 relapsed HL patients
treated at six international centers (Horning et al., 2008). The authors
compared median overall survival, starting at the time of receiving an ASCT,
among ADCETRIS treated patients to patients not treated with ADCETRIS. Key
findings, which were highlighted in a presentation by Dr. Meghan Karuturi from
MD Anderson Cancer Center, included:
*Median overall survival following the date of ASCT in ADCETRIS treated
patients was 91.49 months compared to 27.99 months in those not treated
with ADCETRIS (p<0.0001).
*In an analysis evaluating predictors of patients who achieved a durable
complete remission with ADCETRIS, only the stage of disease at initial
diagnosis had a significant effect on overall survival.
Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL
An investigator-sponsored trial was conducted to evaluate ADCETRIS as a
salvage therapy for HL. Fourteen patients were evaluated for response and
safety and all had relapsed or refractory HL after initial therapy with the
chemotherapy regimens ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine)
or BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin,
procarbazine hydrochloride, prednisone) or a combination of chemotherapy with
or without consolidative radiation treatment. Patients were treated with
ADCETRIS every three weeks for a maximum of four cycles. Data were presented
by Dr. Robert Chen from City of Hope National Medical Center in Duarte, CA.
Data highlights were:
*Of the 14 patients evaluable at the time of this analysis, the objective
response rate was 85.7 percent (12 of 14 patients), including 50 percent
(seven of 14 patients) with a complete remission and 35.7 percent (five of
14 patients) with a partial remission. Two patients achieved stable
disease after four cycles of therapy. No patients developed progressive
disease while on treatment.
*At the time of data analysis, a total of seven of 14 patients had
undergone stem cell mobilization after the fourth dose of ADCETRIS and 100
percent of these patients achieved complete remission after stem cell
transplantation. The other seven patients were still undergoing stem cell
mobilization or had not completed ADCETRIS treatment.
*The most common adverse events of Grade 1 or 2 were peripheral sensory
neuropathy (42.9 percent), rash acneiform (35.7 percent), AST elevation
(28.6 percent) and fatigue (28.6 percent).
*Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract
infection (7.1 percent). There were no Grade 4 adverse events.
ADCETRIS is not approved for salvage HL patients who are deemed eligible for
ASCT. There are multiple ongoing investigator-sponsored trials being conducted
evaluating ADCETRIS as a salvage HL therapy, and a phase I/II clinical trial
evaluating ADCETRIS with bendamustine in this setting will be initiated by the
end of 2012.
Retrospective Analysis of the Safety and Efficacy of Brentuximab Vedotin in
Patients Aged 60 Years or Older with Relapsed or Refractory CD30+ Hematologic
Malignancies (Abstract #3687)
A retrospective analysis was conducted in patients at least 60 years or older
with CD30-positive hematologic malignancies who had received at least one dose
of ADCETRIS in one or more of seven clinical trials. The analysis assessed the
efficacy and safety of single-agent ADCETRIS among 22 systemic anaplastic
large cell lymphoma (sALCL) patients, 16 HL patients and two patients with
other CD30-positive malignancies.
Data highlights from the retrospective analysis of ADCETRIS treated patients
age 60 and older were:
*Of the 40 patients evaluated, 33 patients (83 percent) had an objective
response, including 18 (45 percent) complete remissions and 15 (38
percent) partial remissions.
*Of the 22 patients with sALCL and two patients with other CD30-positive
malignancy, all 24 patients (100 percent) achieved an objective response.
Of the 16 patients with HL, nine patients (56 percent) achieved an
*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.
*The most common adverse events of any grade with an incidence greater than
25 percent were peripheral sensory neuropathy (60 percent), fatigue (58
percent), nausea (38 percent), anemia (30 percent), fever (28 percent),
diarrhea (25 percent) and neutropenia (25 percent).
*The most common Grade 3 or 4 adverse events were neutropenia (25 percent),
anemia (20 percent), peripheral sensory neuropathy (15 percent), fatigue
(10 percent) and thrombocytopenia (10 percent).
ADCETRIS is not approved for the treatment of all CD30-positive hematologic
malignancies. A phase II clinical trial evaluating single-agent ADCETRIS as
front-line therapy for HL patients age 60 and older is currently enrolling
patients. For more information about this clinical trial, visit
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 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+ 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 systemic anaplastic
large cell lymphoma (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 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.
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 II 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 in
the featured 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 these trials 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 September
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
Seattle Genetics, Inc.
Peggy Pinkston, +1-425-527-4160
Tricia Larson, +1-425-527-4180
Press spacebar to pause and continue. Press esc to stop.