-ECHELON-1 Data Anticipated in 2017 to 2018 Timeframe-
BOTHELL, Wash. & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Seattle
Genetics, Inc. (Nasdaq: SGEN) and Takeda
Pharmaceutical Company Limited
(TSE:4502) today announced that the companies have achieved completion
of target patient enrollment in the phase 3 ECHELON-1 clinical trial.
ECHELON-1 is a randomized trial evaluating ADCETRIS (brentuximab
vedotin) as part of a frontline combination chemotherapy regimen in
patients with previously untreated advanced classical Hodgkin lymphoma
(HL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a
defining marker of classical HL. ADCETRIS is currently not approved for
the frontline treatment of HL.
Patients in ECHELON-1 were randomized to receive either ABVD
(Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard
of care for frontline HL, or a novel combination consisting of
ADCETRIS+AVD, which removes bleomycin from the regimen. The trial has
enrolled approximately 1,300 patients, although it remains open at
select sites to complete enrollment of approximately 20 patients in an
additional cohort to fulfill an ex-U.S. regulatory commitment related to
measurement of drug levels during treatment (pharmacokinetics). This
continued enrollment will not affect the expected timing of data readout
from the trial in the 2017 to 2018 timeframe, based on anticipated event
rates. The ECHELON-1 trial is being conducted under a Special Protocol
Assessment (SPA) agreement from the U.S. Food and Drug Administration
(FDA) and the trial also received European Medicines Agency (EMA)
“In the majority of the world, the standard of care for newly diagnosed
Hodgkin lymphoma has not changed in more than three decades, and is
based on the globally recognized ABVD regimen of four chemotherapy
drugs. With the ECHELON-1 clinical trial, our goal is to redefine the
standard of care with a novel ADCETRIS-based combination treatment
regimen that improves patient outcomes with a manageable safety
profile,” said Clay
Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.
“We look forward to reporting results from the ECHELON-1 trial to
potentially support an ADCETRIS supplemental Biologics License
Application seeking a label expansion for use in this setting.”
“Approximately 25 percent of newly diagnosed Hodgkin lymphoma patients
do not respond to initial therapy or relapse within the first two years.
There is a significant need to identify additional potential therapies
in this patient population that may provide a more durable response and
fewer incidences of relapse,” said Dirk Huebner, MD, Global Clinical
Lead, Takeda Oncology.
Data previously presented at the ASH Annual Meeting in 2012 and 2014
from a phase 1 trial evaluating ADCETRIS plus AVD demonstrated that 24
of 25 patients (96 percent) achieved a complete remission. Long-term
follow-up data demonstrated three-year overall survival was 100 percent
and three-year failure-free survival was 92 percent. The most common
adverse events of any grade occurring in more than 30 percent of
patients were neutropenia, nausea, peripheral sensory neuropathy,
fatigue, vomiting, diarrhea, insomnia, bone pain, constipation and hair
ECHELON-1 Trial design
The randomized, open-label, phase 3
trial is investigating ADCETRIS+AVD versus ABVD as frontline therapy in
patients with advanced classical HL. The primary endpoint is modified
progression free survival per independent review facility assessment
using the Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Secondary endpoints include overall survival, complete remission and
safety. The multi-center trial is being conducted in North America,
Europe, South America, Australia, Asia and Africa. The study has
enrolled approximately 1,300 patients who had histologically-confirmed
diagnosis of Stage III or IV classical HL and had not been previously
treated with systemic chemotherapy or radiotherapy. Data from the trial
will be available when a pre-specified number of PFS events have
For more information about the trial, please visit www.clinicaltrials.gov.
About Classical Hodgkin Lymphoma
Lymphoma is a general term
for a group of cancers that originate in the lymphatic system and is the
most common type of blood cancer. There are two major categories of
lymphoma: HL and non-Hodgkin lymphoma. Classical HL is distinguished
from other lymphomas by the characteristic presence of CD30-positive
According to the American Cancer Society, approximately 9,050 cases of
HL will be diagnosed in the United States during 2015 and more than
1,150 will die from the disease.
According to the Lymphoma Coalition, over 62,000 people worldwide are
diagnosed with HL each year and approximately 25,000 people die each
year from this cancer.
ADCETRIS is being evaluated broadly in more
than 30 ongoing clinical trials, including the phase 3 ALCANZA trial and
two additional phase 3 studies, one in frontline classical HL and one in
frontline mature T-cell lymphomas, as well as trials in many additional
types of CD30-expressing malignancies, including B-cell lymphomas.
ADCETRIS 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 has received approval from the FDA
for three indications: (1) regular approval for the treatment of
patients with classical HL after failure of autologous hematopoietic
stem cell transplantation (auto-HSCT) or after failure of at least two
prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates, (2) regular approval for the treatment of
classical HL patients at high risk of relapse or progression as
post-auto-HSCT consolidation, and (3) accelerated approval for the
treatment of patients with systemic anaplastic large cell lymphoma
(sALCL) after failure of at least one prior multi-agent chemotherapy
regimen. The sALCL indication is approved under accelerated approval
based on overall response rate. Continued approval for the sALCL
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory HL and sALCL.
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 55 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 is 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 a CD30-targeted
ADC that, in collaboration with Takeda Pharmaceutical Company Limited,
is commercially available in more than 55 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 in
CD30-expressing malignancies. Seattle Genetics is also advancing a
robust pipeline of clinical-stage programs, including SGN-CD19A,
SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40.
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.
Located in Osaka, Japan, Takeda (TSE:
4502) is a research-based global company with its main focus on
pharmaceuticals. As the largest pharmaceutical company in Japan and one
of the global leaders of the industry, Takeda is committed to strive
towards better health for people worldwide through leading innovation in
medicine. Additional information about Takeda is available through its
corporate website, www.takeda.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® (brentuximab
ADCETRIS is contraindicated with
concomitant bleomycin due to pulmonary toxicity (e.g., interstitial
infiltration and/or inflammation).
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
Anaphylaxis and infusion reactions: Infusion-related reactions,
including anaphylaxis, have occurred with ADCETRIS. Monitor patients
during infusion. If an infusion-related reaction occurs, interrupt the
infusion and institute appropriate medical management. If anaphylaxis
occurs, immediately and permanently discontinue the infusion and
administer appropriate medical therapy.
Hematologic toxicities: Prolonged (≥1 week) severe neutropenia
and Grade 3 or 4 thrombocytopenia or anemia 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. Monitor
patients for fever. If Grade 3 or 4 neutropenia develops, consider
dose delays, reductions, discontinuation, or G-CSF prophylaxis with
Serious infections and opportunistic infections: Infections
such as pneumonia, bacteremia, and sepsis or 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.
Increased toxicity in the presence of severe renal impairment: The
frequency of ≥Grade 3 adverse reactions and deaths was greater in
patients with severe renal impairment compared to patients with normal
renal function. Avoid the use of ADCETRIS in patients with severe
Increased toxicity in the presence of moderate or severe hepatic
impairment: The frequency of ≥Grade 3 adverse reactions and deaths
was greater in patients with moderate or severe hepatic impairment
compared to patients with normal hepatic function. Avoid the use of
ADCETRIS in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Serious cases of hepatotoxicity, including
fatal outcomes, have occurred with ADCETRIS. Cases were consistent
with hepatocellular injury, including elevations of transaminases
and/or bilirubin, and occurred after the first dose of ADCETRIS or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may also increase the risk.
Monitor liver enzymes and bilirubin. Patients experiencing new,
worsening, or recurrent hepatotoxicity may require a delay, change in
dose, or discontinuation of ADCETRIS.
Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death has been reported in
ADCETRIS-treated patients. First onset of symptoms occurred at various
times from initiation of ADCETRIS therapy, with some cases occurring
within 3 months of initial exposure. 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. Hold ADCETRIS if PML
is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary Toxicity: Events of noninfectious pulmonary toxicity
including pneumonitis, interstitial lung disease, and acute
respiratory distress syndrome, some with fatal outcomes, have been
reported. Monitor patients for signs and symptoms of pulmonary
toxicity, including cough and dyspnea. In the event of new or
worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation
and until symptomatic improvement.
Serious dermatologic reactions: Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN), including fatal outcomes, have
been reported with ADCETRIS. If SJS or TEN occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant
women of the potential hazard to the fetus.
Most Common Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients with relapsed
classical HL and sALCL in two uncontrolled single-arm 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.
ADCETRIS was studied in 329 patients with classical HL at high risk of
relapse or progression post-auto-HSCT in a placebo-controlled randomized
trial. The most common adverse reactions (≥20%) in the
ADCETRIS-treatment arm (167 patients), regardless of causality, were
neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia,
upper respiratory tract infection, fatigue, peripheral motor neuropathy,
nausea, cough, and diarrhea.
Concomitant use of strong CYP3A4
inhibitors or inducers, or P-gp inhibitors, has the potential to affect
the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse
reactions are increased in patients with moderate or severe hepatic
impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING,
please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.
ADCETRIS Global Important Safety Information
ADCETRIS® is indicated for the treatment of adult patients with relapsed
or refractory (r/r) CD30+ Hodgkin lymphoma:
1. Following autologous stem cell transplant or
2. Following at least 2 prior therapies when autologous stem cell
transplantation is not a treatment option
ADCETRIS is indicated for the treatment of adult patients with relapsed
or refractory systemic anaplastic large cell lymphoma (sALCL).
ADCETRIS is contraindicated for patients who are hypersensitive to
ADCETRIS. In addition, combined use of bleomycin and ADCETRIS causes
pulmonary toxicity, and is contraindicated.
ADCETRIS can cause serious side effects, including:
Progressive multifocal leukoencephalopathy (PML): John
Cunningham virus (JCV) reactivation resulting in PML and death has
been reported in patients treated with ADCETRIS. Patients should be
closely monitored for new or worsening neurological, cognitive, or
behavioral signs or symptoms, which may be suggestive of PML.
Pancreatitis: Acute pancreatitis has been observed in patients
treated with ADCETRIS. Fatal outcomes have been reported. Patients
should be closely monitored for new or worsening abdominal pain.
Pulmonary Toxicity: Cases of pulmonary toxicity have been
reported in patients receiving ADCETRIS. In the event of new or
worsening pulmonary symptoms (e.g., cough, dyspnoea), a prompt
diagnostic evaluation should be performed.
Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteraemia,
sepsis/septic shock (including fatal outcomes), and herpes zoster, and
opportunistic infections such as Pneumocystis jiroveci pneumonia and
oral candidiasis have been reported in patients treated with ADCETRIS.
Patients should be carefully monitored during treatment for emergence
of possible serious and opportunistic infections.
Infusion-related reactions: Immediate and delayed
infusion-related reactions, as well as anaphylaxis, have occurred with
ADCETRIS. Patients should be carefully monitored during and after an
Tumor lysis syndrome (TLS): TLS has been reported with
ADCETRIS. Patients with rapidly proliferating tumor and high tumor
burden are at risk of TLS and should be monitored closely and managed
according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause PN
that is predominantly sensory. Cases of peripheral motor neuropathy
have also been reported. Patients should be monitored for symptoms of
PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain, or weakness.
Hematological toxicities: Grade 3 or Grade 4 anemia,
thrombocytopenia, and prolonged (equal to or greater than one week)
Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood
counts should be monitored prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia has been reported.
Patients should be monitored closely for fever and managed according
to best medical practice.
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): SJS
and TEN have been reported. Fatal outcomes have been reported.
Hyperglycemia: Hyperglycemia has been reported during trials in
patients with an elevated body mass index (BMI) with or without a
history of diabetes mellitus. Any patient who experiences an event of
hyperglycemia should have their serum glucose closely monitored.
Renal and hepatic impairment: There is limited experience
in patients with renal and hepatic impairment. Population
pharmacokinetic analysis indicated that MMAE clearance might be
affected by moderate and severe renal impairment, and by low serum
albumin concentrations. Elevations in alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) have been reported. Liver
function should be routinely monitored in patients receiving
Sodium content in excipients: This medicinal product contains a
maximum of 2.1 mmol (or 47mg) of sodium per dose. To be taken into
consideration for patients on a controlled sodium diet.
Serious adverse drug reactions were: neutropenia, thrombocytopenia,
constipation, diarrhea, vomiting, pyrexia, peripheral motor neuropathy
and peripheral sensory neuropathy, hyperglycemia, demyelinating
polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
ADCETRIS was studied as monotherapy in 160 patients in two Phase 2
studies. Across both studies, adverse reactions defined as very common
(≥1/10) were: infections, neutropenia, peripheral sensory neuropathy,
diarrhea, nausea, vomiting, alopecia, pruritis, myalgia, fatigue,
pyrexia, and infusion-related reactions. Adverse reactions defined as
common (≥1/100 to <1/10) were: upper respiratory tract infection, herpes
zoster, pneumonia, anemia, thrombocytopenia, hyperglycemia, peripheral
motor neuropathy, dizziness, demyelinating polyneuropathy, cough,
dyspnea, constipation, rash, arthralgia, back pain, and chills.
These are not all of the possible side effects with ADCETRIS. Please
refer to Summary of Product Characteristics (SmPC) before prescribing.
For Seattle Genetics Forward-Looking Statement:
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic and
commercial potential of ADCETRIS, including ADCETRIS’ potential as a
treatment for advanced classical HL, the anticipated timing of data from
the ECHELON-1 trial, the anticipated benefits of Seattle Genetics’
ADCETRIS clinical development program, and the potential submission of a
supplemental Biologics License Application seeking a label expansion for
ADCETRIS use in the ECHELON-1 setting. 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 risks of adverse events associated with ADCETRIS use,
negative or unexpected ADCETRIS clinical trial results even after
promising results in earlier company- and investigator-sponsored trials,
and adverse regulatory actions affecting ADCETRIS, all of which could
result in Seattle Genetics being unable to expand ADCETRIS’ labeled
indications of use to the ECHELON-1 or any other settings. Seattle
Genetics may also experience delays in the conduct of and obtaining data
from the ECHELON-1 and its other clinical trials, in each case for a
variety of reasons, including the inherent difficulty and uncertainty of
pharmaceutical product development. More information about the risks and
uncertainties faced by Seattle Genetics is contained under the caption
“Risk Factors” included in Exhibit 99.1 to the company’s Current Report
on Form 8-K filed with the Securities and Exchange Commission on
September 9, 2015. 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.
Peggy Pinkston, 425-527-4160
Tsuyoshi Tada, +81 (0) 3-3278-2417
Elizabeth Pingpank, +1-617-444-1495