-FDA Approval Based on the Phase 3 AETHERA Clinical Trial Results-
-AETHERA Trial Also Converts Prior Accelerated Approval to Regular
Approval in Treatment of Classical Hodgkin Lymphoma Patients who Fail
Autologous Hematopoietic Transplantation or who Fail at Least Two Prior
Multi-Agent Chemotherapy Regimens and are Not Autologous Hematopoietic
-Label Expansion Represents Third Indication for ADCETRIS in the U.S.
and the First of Four Phase 3 Clinical Trials Intended to Broaden the
Global Use of ADCETRIS in CD30-Expressing Lymphomas-
-ADCETRIS is the Only FDA-Approved Therapy to Prolong
Progression-Free Survival Following Autologous Hematopoietic
Transplantation in Classical Hodgkin Lymphoma-
BOTHELL, Wash.--(BUSINESS WIRE)--Aug. 17, 2015--
Genetics, Inc. (Nasdaq: SGEN) announced today that the U.S. Food and
Drug Administration (FDA) has approved ADCETRIS (brentuximab vedotin)
for the treatment of patients with classical Hodgkin lymphoma (HL) at
high risk of relapse or progression as post-autologous hematopoietic
stem cell transplantation (auto-HSCT) consolidation. The approval is
based on a phase 3 clinical trial called AETHERA that was designed to
compare up to 16 cycles (approximately one year) of ADCETRIS therapy
administered every three weeks following auto-HSCT to placebo. The
primary endpoint was met with a significant improvement in median
progression-free survival (PFS) of 42.9 months (95% CI: 30.4, 42.9) for
patients who received ADCETRIS versus 24.1 months (95% CI: 11.5, not
estimable) for patients who received placebo, an improvement of 18.8
months (hazard ratio=0.57 [95% CI: 0.40, 0.81]; p-value=0.001). In
addition, data from the AETHERA trial converted the U.S. accelerated
approval of the relapsed classical HL indication to regular approval.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is
expressed in classical HL and systemic anaplastic large cell lymphoma
(sALCL), as well as other lymphoma subtypes. This is the third
indication for ADCETRIS, which was granted accelerated FDA approval in
August 2011 for two other indications: (1) treatment of Hodgkin lymphoma
patients who fail autologous transplant or who fail at least two prior
multi-agent chemotherapy regimens and are not autologous transplant
candidates, and (2) treatment of systemic ALCL patients who fail at
least one prior multi-agent chemotherapy regimen. The sALCL indication
is approved under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials.
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Globally, there are more than 65,000 cases of HL diagnosed each year.
Although frontline combination chemotherapy can result in durable
responses, up to 30 percent of these patients fail frontline treatment.
The standard for these patients is salvage therapy, followed by
auto-HSCT; approximately half of all HL patients who undergo an
auto-HSCT experience subsequent disease relapse.
“With this FDA approval, ADCETRIS is the first and only consolidation
treatment option available to high risk classical Hodgkin lymphoma
patients who undergo a transplant to preserve their post-auto-HSCT
remissions,” said Clay
Siegall, Ph.D., President and Chief Executive Officer of Seattle
Genetics. “This represents a meaningful advance for cancer patients and
an important milestone for the ADCETRIS development program. Together
with our three ongoing phase 3 trials and more than 30 additional
clinical trials, this approval supports our goal to broadly establish
ADCETRIS as the foundation of therapy for classical Hodgkin lymphoma and
“The FDA approval of brentuximab vedotin for post-autologous
hematopoietic transplantation consolidation treatment in classical
Hodgkin lymphoma patients with high risk of relapse or progression is a
significant milestone for patients and physicians,” said Craig
Moskowitz, M.D., lead investigator on the trial and Clinical Director,
Division of Hematologic Oncology, Memorial Sloan Kettering Cancer
Center. “Approximately half of all Hodgkin lymphoma patients who undergo
an autologous hematopoietic stem cell transplant will relapse,
representing a significant need for additional treatment options to
improve progression free survival.”
AETHERA Phase 3 Trial Demonstrates Significant Progression-Free
Survival Benefit with ADCETRIS as Post-Transplant Consolidation in
The positive results from the phase 3 AETHERA trial were published in The
Lancet in March 2015 and presented at the 56th American
Society of Hematology (ASH) Annual Meeting in December 2014. A total of
329 HL patients at risk of relapse or progression were enrolled,
including 165 on the ADCETRIS arm and 164 on the placebo arm. Patients
eligible for enrollment in the AETHERA trial must have had a history of
primary refractory HL, have relapsed within one year from receiving
frontline chemotherapy and/or have had disease outside of the lymph
nodes at the time of pre-auto-HSCT relapse. Results included:
The trial achieved its primary endpoint and demonstrated a significant
increase in PFS per independent review facility, with a hazard ratio
of 0.57 (95% CI: 0.40, 0.81) and a p-value of 0.001. Median PFS was 43
months (95% CI: 30.4, 42.9) for patients who received ADCETRIS versus
24 months (95% CI: 11.5, not estimable) for patients who received
The most common adverse events (≥20 percent), of any grade and
regardless of causality, in the ADCETRIS arm were neutropenia (78
percent), peripheral sensory neuropathy (56 percent), thrombocytopenia
(41 percent), anemia (27 percent), upper respiratory tract infection
(26 percent), fatigue (24 percent), peripheral motor neuropathy (23
percent), nausea (22 percent), cough (21 percent) and diarrhea (20
percent). The most common adverse events (≥20 percent), of any grade
and regardless of causality, in the placebo arm were neutropenia (34
percent), upper respiratory tract infection (23 percent) and
thrombocytopenia (20 percent). Sixty-seven percent of patients on the
ADCETRIS arm experienced peripheral neuropathy. Of those patients, 85
percent had resolution (59 percent) or partial improvement (26
percent) in symptoms at the time of their last evaluation, with a
median time to improvement of 23 weeks (range 0.1-138).
There are no post-marketing requirements as part of the U.S. approval.
The AETHERA data have also been submitted to both the European Medicines
Agency (EMA) and Health Canada requesting marketing authorization.
As part of a broad clinical development program, ADCETRIS is also being
evaluated in three additional phase 3 clinical trials, referred to as
ECHELON-1, ECHELON-2 and ALCANZA. Enrollment is expected to be completed
in ECHELON-1 and ALCANZA during 2015 and in ECHELON-2 during 2016.
ADCETRIS is being evaluated broadly in more than 30 ongoing clinical
trials, including three additional phase 3 studies, in earlier lines of
its approved classical HL and sALCL indications as well as in many
additional types of CD30-positive malignancies, including cutaneous
T-cell lymphoma, B-cell lymphomas and mature T-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 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 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
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 more than 55
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 is solely responsible for development costs.
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®
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
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.
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 Reed-Sternberg cells. The Reed-Sternberg cell generally
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.
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.
Forward Looking Statements
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, the anticipated benefits of Seattle
Genetics’ ADCETRIS clinical development program and expected enrollment
completion in Seattle Genetics’ ADCETRIS phase 3 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 risk of adverse events associated with ADCETRIS
use, negative or unexpected ADCETRIS clinical trial results and adverse
regulatory actions affecting ADCETRIS, all of which could result in
Seattle Genetics being unable to broaden the use of ADCETRIS. Seattle
Genetics may also experience delays in the enrollment in and conduct of
its clinical trials, and obtaining data from its clinical trials, in
each case for a variety of reasons, including the difficulty and
uncertainty of pharmaceutical product development. More information
about the risks and uncertainties faced by Seattle Genetics is contained
in the company’s Quarterly Report on Form 10-Q for the quarter ended
June 30, 2015 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20150817006214/en/
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160