BOTHELL, Wash. & OSAKA, Japan - Wednesday, October 1st 2014 [ME NewsWire]
Randomized Phase 3 Clinical Trial with ADCETRIS Demonstrates Statistically Significant Improvement in Progression-Free Survival
Abstract Submitted to ASH for Presentation at the 2014 Annual Meeting; Regulatory Submissions Anticipated in 2015
Seattle Genetics to Host Conference Call and Webcast Today at 8:30 a.m. ET
ASH 2014
(BUSINESS
WIRE)-- Seattle Genetics, Inc. (Nasdaq: SGEN) and Takeda Pharmaceutical
Company Limited (TSE:4502) today announced that patients with Hodgkin
lymphoma (HL) who received ADCETRIS (brentuximab vedotin) as
consolidation therapy immediately following an autologous stem cell
transplantation (ASCT) lived significantly longer without disease
progression compared to patients who received placebo. The phase 3
clinical trial, known as AETHERA, compared the use of single agent
ADCETRIS to placebo in 329 patients with HL who were at risk of relapse.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a
defining marker of classical HL. ADCETRIS has been approved in more than
45 countries for the treatment of relapsed HL and systemic anaplastic
large cell lymphoma (sALCL). ADCETRIS is not approved in the AETHERA
treatment setting.
The AETHERA trial met its primary endpoint with
ADCETRIS treatment resulting in a statistically significant improvement
in progression-free survival (PFS) versus placebo as assessed by an
independent central review committee (hazard ratio=0.57; p-value=0.001),
which equates to a 75 percent improvement in PFS. PFS was assessed
after a minimum of two years post initiation of treatment for all study
patients. A pre-specified interim analysis of overall survival showed no
statistically significant difference between the treatment arms.
Patients on both study arms with progression of HL received a variety of
subsequent therapies. Notably, most patients on the placebo arm
received ADCETRIS after progression. A further analysis of overall
survival is planned in 2016. The safety profile of ADCETRIS in the
AETHERA trial was generally consistent with the existing prescribing
information. An abstract was previously submitted for data presentation
at the American Society of Hematology (ASH) annual meeting, December
6-9, 2014, in San Francisco, CA.
“Patients with Hodgkin lymphoma who
relapse or are refractory to frontline therapy represent a significant
unmet medical need. We believe the positive top-line results of the
AETHERA trial demonstrate the ability of ADCETRIS to consolidate
remissions and extend progression-free survival in patients with Hodgkin
lymphoma who are at risk of relapse following an autologous transplant
while having an acceptable safety profile,” said Clay B. Siegall, Ph.D.,
President and Chief Executive Officer of Seattle Genetics. “We
anticipate reporting more complete AETHERA data at the ASH annual
meeting in December and intend to submit a supplemental Biologics
License Application to the FDA in 2015 for approval in this setting.”
“The
AETHERA clinical trial results may support a new treatment paradigm for
certain patients with Hodgkin lymphoma post autologous stem cell
transplant,” said Michael Vasconcelles, M.D., Global Head, Oncology
Therapeutic Area Unit, Takeda Pharmaceutical Company. “As the first
randomized clinical trial of a comprehensive clinical development
program with ADCETRIS, these data also provide important information to
inform the entire ADCETRIS program. For these reasons, we are
particularly grateful to the patients, in partnership with their
families and the study investigators, for their participation in
AETHERA. We look forward to submitting these data to regulatory agencies
in our territories.”
Phase 3 AETHERA Clinical Trial Design The
AETHERA trial is a randomized, double-blind, placebo-controlled phase 3
study designed to evaluate the potential of ADCETRIS to extend PFS
post-ASCT in patients with HL who have at least one risk factor for
progression. In addition to the primary endpoint of PFS, secondary
endpoints included overall survival, safety and tolerability. Patients
must have risk factors for residual HL, defined as a history of
refractory HL, those who relapse or progress within one year from
receiving frontline chemotherapy and/or those who have disease outside
of the lymph nodes at the time of pre-ASCT relapse. Patients received
ADCETRIS or placebo every three weeks for up to approximately one year.
This international multi-center trial is being conducted in the United
States, Eastern and Western Europe and Russia.
Submission of safety
data from the AETHERA trial to the FDA is a post-marketing requirement
that Seattle Genetics will fulfill in its planned supplemental BLA.
Takeda will provide safety data from the trial to the European Medicines
Agency (EMA) as part of periodic safety reports required by the EMA’s
conditional approval of ADCETRIS.
Please see Important Safety Information at the end of this press release.
Seattle
Genetics Conference Call Details Seattle Genetics' management will host
a conference call and webcast to discuss this announcement. The event
will be held today at 5:30 a.m. Pacific Time (PT) / 8:30 a.m. Eastern
Time (ET). The live event will be available from Seattle Genetics'
website at http://www.seattlegenetics.com, under the Investors and News
section, or by calling 888-455-2263 (domestic) or 719-325-2464
(international). The access code is 9378967. A replay of the discussion
will be available beginning at approximately 7:00 a.m. PT / 10:00 a.m.
ET today from Seattle Genetics' website or by calling 888-203-1112
(domestic) or 719-457-0820 (international), using access code 9378967.
The telephone replay will be available until 8:30 a.m. PT / 11:30 a.m.
ET October 1, 2014.
About ADCETRIS 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 U.S. Food and Drug Administration
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 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 45 countries. See important safety information
below.
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 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: HL and non-Hodgkin lymphoma. HL 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.
According to the
American Cancer Society, approximately 9,200 cases of HL will be
diagnosed in the United States during 2014 and more than 1,200 will die
from the disease. Globally, there are more than 62,000 cases of HL
diagnosed each year. Although frontline combination chemotherapy can
result in durable response rates, up to 30 percent of these patients
relapse or are refractory to frontline treatment and have few
therapeutic options beyond ASCT.
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, is commercially available for two indications in more
than 45 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-CD19A,
SGN-CD33A, SGN-LIV1A, SGN-CD70A, 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.
About
Takeda Located in Osaka, Japan, Takeda 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
BOXED
WARNING Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death can occur in patients receiving
ADCETRIS.
Contraindication: Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
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 modifications accordingly.
Infusion
reactions: Infusion-related reactions, including anaphylaxis, have
occurred with ADCETRIS. Monitor patients during infusion. If an infusion
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: 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 therapy.
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.
Adverse
Reactions: 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.
Drug
Interactions: 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. Closely monitor these
patients 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
orwww.ADCETRIS.com.
ADCETRIS Global Important Safety Information
ADCETRIS® is indicated for the treatment of adult patients with relapsed
or refractory (r/r) CD30+ Hodgkin lymphoma (HL):
Following autologous stem cell transplant or
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 infusion.
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 brentuximab vedotin.
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: 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 plans for
submission for supplemental regulatory approval to and obtaining
regulatory approval from the FDA. 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 safety and/or efficacy results of the AETHERA trial in high
risk, post-ASCT Hodgkin lymphoma will not be sufficient to gain
marketing approval in the United States or any other country, that we
will be required to amend our submission for marketing approval or that
such submission will be refused. In addition, our regulatory plans may
change as a result of consultation with the FDA. 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, 2014 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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Contacts
Seattle Genetics
Investors:
Peggy Pinkston, 425-527-4160
ppinkston@seagen.com
OR
Media:
Tricia Larson, 425-527-4180
tlarson@seagen.com
OR
Takeda
Millennium: The Takeda Oncology Company
Elizabeth Pingpank, +1-617-444-1495
elizabeth.pingpank@takeda.com
OR
Takeda Pharmaceutical Company Limited
Corporate Communications Department
+81-3-3278-2037
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