|[February 27, 2014]
Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Clinical Data at the 2014 Bone Marrow Transplant Tandem Meetings
BOTHELL, Wash. --(Business Wire)--
Genetics, Inc. (NASDAQ:SGEN) today highlighted ADCETRIS (brentuximab
vedotin) data at the 2014 Bone Marrow Transplant (BMT) Tandem Meetings
being held February 26 to March 2, 2014, in Dallas, Texas. Presentations
included the first report from an ongoing phase 1/2 clinical trial
evaluating the combination of ADCETRIS and bendamustine in the treatment
of salvage Hodgkin lymphoma (HL). In addition, a poster presentation
summarized the clinical trial design and pooled patient demographics
from the phase 3 AETHERA trial in patients with increased risk factors
for HL progression following autologous stem cell transplant (ASCT).
ADCETRIS is an antibody-drug conjugate (ADC (News - Alert)) directed to CD30, which is
expressed in classical HL and systemic anaplastic large cell lymphoma
"We are focused on exploring the potential to improve outcomes in
earlier lines of HL by incorporating ADCETRIS in novel settings, and the
data presented at the 2014 BMT Tandem Meetings illustrate this goal,"
said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice
President, Research and Development, at Seattle Genetics. "The interim
data presented today evaluating ADCETRIS and bendamustine combination
therapy in the salvage HL setting are encouraging, showing a complete
remission rate of 77 percent, with another 15 percent of patients, who
currently remain on treatment, achieving early partial remissions. In
addition, a pooled analysis for the overall population in the AETHERA
phase 3 clinical trial was presented, including demographic data,
baseline disease characteristics and treatment exposure. We look forward
to presenting efficacy and safety data from the AETHERA trial in the
second half of 2014."
A Phase 1/2 Single-Arm, Open-Label Study to Evaluate the Safety and
Efficacy of Brentuximab Vedotin in Combination with Bendamustine for
Patients with Hodgkin Lymphoma in the First Salvage Setting: Interim
Results (Abstract #230, poster presentation on Wednesday, February 26,
2014, at 6:45 PM CT)
Interim data from an ongoing phase 1/2 clinical trial were reported from
23 patients with HL after first relapse. The multi-phase study was
divided into two cohorts to determine the recommended dose and
tolerability of ADCETRIS in combination with bendamustine and to assess
the complete remission rate associated with combination use.
Bendamustine is an alkylating agent used in the treatment of chronic
lymphocytic leukemias and lymphomas. In this trial, patients are
eligible to receive up to six cycles of ADCETRIS in combination with
bendamustine followed by additional single-agent ADCETRIS for a total of
16 cycles. As a part of the trial design, after patients receive
ADCETRIS plus bendamustine combination therapy, they have the option to
pause therapy to receive an ASCT and then resume treatment with
single-agent ADCETRIS as consolidation. The median age of patients
enrolled in the trial was 43 years. At the time of data analysis, 23
patients were evaluable for safety and 13 were evaluable for response.
Key findings include:
After a median of two cycles of therapy, 92 percent of patients
evaluable for response (12 of 13 patients) achieved an objective
response, including 77 percent (ten patients) with complete remissions
and 15 percent (two patients) with partial remissions. At the time of
analysis, the two patients with partial remissions had each received
two cycles of therapy and treatment was ongoing.
At the time of the analysis, seven patients had undergone an ASCT and
three had restarted ADCETRIS as monotherapy.
The most common adverse events were nausea (57 percent), rash (39
percent), fever (35 percent), fatigue (30 percent) and vomiting (30
The most common Grade 3 or 4 adverse event was lymphopenia (13 percent
Grade 3; nine percent Grade 4).
Infusion reactions considered related to combination therapy were
reported as serious adverse events in six patients and led to
treatment discontinuation for three patients. Symptoms included rash,
hives, itching, shortness of breath, wheezing, throat tightness,
fever, chills and hypotension. As a result, the protocol is being
amended to require premedication with corticosteroids and
Enrollment is ongoing to include up to 50 patients at multiple centers
in the United States. For more information about this trial, visit www.clinicaltrials.gov.
ADCETRIS is not approved for salvage HL patients who are deemed eligible
The AETHERA Trial: An Ongoing Phase 3 Study of Brentuximab Vedotin in
the Treatment of Patients at High Risk of Residual Hodgkin Lymphoma
Following Autologous Stem Cell Transplant (Abstract #148, poster
presentation on Wednesday, February 26, 2014, at 6:45 PM CT)
The AETHERA clinical trial is a randomized, double-blind,
placebo-controlled phase 3 study designed to evaluate the potential of
DCETRIS to prevent progression post-ASCT in patients with at least one
risk factor for lymphoma progression. The primary endpoint is
progression-free survival. Randomization was stratified by risk factors
at the time of initiating salvage therapy (refractory, relapsed within
12 months or relapsed after 12 months with extranodal involvement) and
by response to salvage therapy (complete remission, partial remission or
stable disease). The poster presentation reviewed the demographics and
baseline disease characteristics of the 329 patients who enrolled in the
study. Key findings for the pooled, blinded data include:
Regarding response to frontline therapy, 196 patients (60 percent)
were refractory, 107 patients (33 percent) relapsed in less than 12
months and 26 patients (eight percent) relapsed after more than 12
months with extranodal disease.
Regarding response to salvage treatment pre-ASCT, 125 patients (38
percent) had a complete remission, 111 patients (34 percent) had a
partial remission and 93 patients (28 percent) had stable disease.
The median number of treatment cycles was 15 (range, 1-16), and
approximately half of all patients (49 percent) received the maximum
16 cycles of study treatment.
All patients had completed or discontinued treatment as of August
2013; 61 patients (19 percent) discontinued treatment due to an
Forty-two patients (13 percent) are known to have died, including 37
deaths that occurred after disease progression and one death that
occurred within 30 days of the last dose and was considered not
The primary efficacy analysis of the AETHERA phase 3 clinical trial
will be reported in the second half of 2014.
ADCETRIS is not approved for HL patients prior to relapse following ASCT.
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 for intravenous injection received accelerated approval from
the FDA and approval with conditions from Health Canada for two
indications: (1) the treatment of patients with HL 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 two indications: (1) for the treatment of
adult patients with relapsed or refractory CD30-positive HL following
autologous stem cell transplant (ASCT), or following at least two prior
therapies when ASCT or multi-agent chemotherapy is not a treatment
option, and (2) the treatment of adult patients with relapsed or
refractory sALCL. ADCETRIS has received marketing authorization by
regulatory authorities in more than 35 countries. See important safety
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the
terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and Takeda 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 Takeda will be solely responsible for development costs.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development
and commercialization of innovative antibody-based therapies for the
treatment of cancer. Seattle Genetics is leading the field in developing
antibody-drug conjugates (ADCs), a technology designed to harness the
targeting ability of antibodies to deliver cell-killing agents directly
to cancer cells. The company's lead product, ADCETRIS®
(brentuximab vedotin), is an ADC that, in collaboration with Takeda
Pharmaceutical Company Limited, has been approved for two indications in
more than 35 countries, including the U.S., Canada, Japan and members of
the European Union. Additionally, ADCETRIS is being evaluated broadly in
more than 30 ongoing clinical trials. Seattle Genetics is also advancing
a robust pipeline of clinical-stage ADC programs, including SGN (News - Alert)-CD19A,
SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. 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, Genentech, GlaxoSmithKline and
Pfizer. More information can be found at www.seattlegenetics.com.
ADCETRIS (brentuximab vedotin) 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. Monitor patients for symptoms of neuropathy,
such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain or weakness and institute dose
Infusion reactions: Infusion-related reactions, including anaphylaxis,
have occurred with ADCETRIS. Monitor patients during infusion. If an
infusion reaction occurs, interrupt the infusion. If anaphylaxis
occurs, immediately and permanently discontinue the infusion.
Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and
prolonged (=1 week) severe neutropenia can occur with ADCETRIS.
Febrile neutropenia has been reported with ADCETRIS. Monitor complete
blood counts prior to each dose of ADCETRIS and consider more frequent
monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor
patients for fever. If Grade 3 or 4 neutropenia develops, manage by
G-CSF support, dose delays, reductions or discontinuation.
Serious infections and opportunistic infections: Infections such as
pneumonia, bacteremia and sepsis/septic shock (including fatal
outcomes) have been reported in patients treated with ADCETRIS.
Closely monitor patients during treatment for the emergence of
possible bacterial, fungal or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly
proliferating tumor and high tumor burden.
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 (SJS): SJS has been reported with ADCETRIS.
If SJS occurs, discontinue ADCETRIS and administer appropriate medical
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women 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.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp
inhibitors, has the potential to affect the exposure to MMAE.
Use in Specific Populations:
MMAE exposure is increased in patients with hepatic impairment and
severe renal impairment.
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 therapeutic
potential of ADCETRIS and initiation of future 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 efficacy in these
clinical trials for Hodgkin lymphoma and the risk of adverse events as
ADCETRIS advances in other 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, 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.
[ InfoTech Spotlight's Homepage ]