-PDUFA Action Date May 1, 2018-
-Submission Based on Positive Results from the
Phase 3 ECHELON-1 Clinical Trial-
-FDA Previously Granted Breakthrough Therapy
Designation for ADCETRIS in Frontline Advanced Hodgkin
Lymphoma-
Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that the
U.S. Food and Drug Administration (FDA) has accepted for filing a
supplemental Biologics License Application (BLA) for ADCETRIS
(brentuximab vedotin) in combination with chemotherapy for the
frontline treatment of patients with advanced classical Hodgkin
lymphoma. The FDA granted Priority Review for the application, and
the Prescription Drug User Fee Act (PDUFA) target action date is
May 1, 2018. The submission of the supplemental BLA is based on
positive results from a phase 3 clinical trial called ECHELON-1
that was designed to determine if ADCETRIS in combination with
chemotherapy could extend modified progression-free survival
(modified PFS) in previously untreated advanced classical Hodgkin
lymphoma patients. ADCETRIS is an antibody-drug conjugate (ADC)
directed to CD30, a defining marker of classical Hodgkin lymphoma.
ADCETRIS is being evaluated globally as the foundation of care for
CD30-expressing lymphomas in more than 70 corporate- and
investigator-sponsored clinical trials. ADCETRIS is currently not
approved as a frontline therapy for Hodgkin lymphoma.
“The FDA’s filing of our supplemental BLA with Priority Review
represents a significant milestone in our goal to redefine the
frontline treatment of advanced Hodgkin lymphoma,” said Clay
Siegall, Ph.D., President and Chief Executive Officer of Seattle
Genetics. “We recently reported the primary data from the phase 3
ECHELON-1 clinical trial in the Plenary Scientific Session of the
2017 ASH Annual Meeting with simultaneous publication in the New
England Journal of Medicine. The data demonstrated superior
activity of the ADCETRIS-containing regimen over standard of care,
and we are working with the FDA to make this bleomycin-free regimen
available to newly diagnosed advanced Hodgkin lymphoma patients as
soon as possible.”
In October 2017, the FDA granted ADCETRIS Breakthrough Therapy
Designation based on the ECHELON-1 study results. The FDA’s
Breakthrough Therapy Designation is intended to expedite the
development and review of promising drug candidates for serious or
life-threatening conditions. It is based upon clinical evidence of
substantial improvement over existing therapies in one or more
clinically significant endpoints.
The ECHELON-1 study evaluated a combination of ADCETRIS plus AVD
(Adriamycin, vinblastine, dacarbazine) compared to a recognized
standard of care chemotherapy regimen, ABVD (which includes
bleomycin), in frontline advanced classical Hodgkin lymphoma. The
positive results from the phase 3 ECHELON-1 trial were featured in
the Plenary Scientific Session of the 59th American Society of
Hematology (ASH) Annual Meeting with simultaneous publication in
the New England Journal of Medicine in December 2017. Results from
the ECHELON-1 trial in 1,334 Hodgkin lymphoma patients
included:
- The trial achieved its primary endpoint
with the combination of ADCETRIS plus AVD resulting in a
statistically significant improvement in modified PFS versus the
control arm of ABVD as assessed by an Independent Review Facility
(IRF) (p-value=0.035). This corresponds to a 23 percent reduction
in the risk of progression, death or need for additional anticancer
therapy. Per IRF assessment, the two-year modified PFS rate for
patients in the ADCETRIS plus AVD arm was 82.1 percent compared to
77.2 percent in the control arm.
- The investigator assessment of modified
PFS also demonstrated a statistically significant advantage
for ADCETRIS plus AVD versus the control arm of ABVD
(p-value <0.01).
- All secondary endpoints, including
interim analysis of overall survival, trended in favor of the
ADCETRIS plus AVD arm.
- The safety profile of ADCETRIS plus AVD
in the ECHELON-1 trial was generally consistent with that known for
the single-agent components of the regimen.
ECHELON-1 Phase 3 Clinical Trial DesignThe randomized,
open-label, phase 3 trial is investigating ADCETRIS plus AVD versus
ABVD as frontline therapy in patients with advanced classical
Hodgkin lymphoma. The primary endpoint is modified PFS per
Independent Review Facility assessment using the Revised Response
Criteria for Malignant Lymphoma. Modified PFS is defined as the
time to progression, death or receipt of additional anticancer
therapy for patients who are not in complete response after
completion of frontline therapy per Independent Review Facility.
Secondary endpoints include overall survival, complete remission
and safety. The multi-center trial was conducted in North America,
Europe, South America, Australia, Asia and Africa. The study
enrolled 1,334 patients who had a histologically-confirmed
diagnosis of Stage III or IV classical Hodgkin lymphoma and had not
been previously treated with systemic chemotherapy or radiotherapy.
The ECHELON-1 trial was conducted under a Special Protocol
Assessment (SPA) agreement from the FDA and the trial also received
EMA scientific advice.
Please see Important Safety Information at the end of this press
release.
About Classical Hodgkin LymphomaLymphoma 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. Classical 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 expresses CD30. Although the currently used standard of care
frontline combination chemotherapy can result in durable responses,
up to 30 percent of patients with advanced Hodgkin lymphoma relapse
or are refractory to frontline treatment.
According to the American Cancer Society, approximately 8,260
cases of Hodgkin lymphoma will be diagnosed in the United States
during 2017 and more than 1,000 will die from the disease.
According to the Lymphoma Coalition, over 62,000 people (including
early and advanced stage) worldwide are diagnosed with Hodgkin
lymphoma each year and approximately 25,000 people die each year
from this cancer.
About ADCETRISADCETRIS is being evaluated broadly in more
than 70 clinical trials, including three phase 3 studies: the
completed ECHELON-1 trial in frontline classical Hodgkin lymphoma
that supported the recent FDA Breakthrough Therapy Designation and
submission of the supplemental Biologics License Application (BLA)
for use in this setting, the ongoing ECHELON-2 trial in frontline
mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of
ADCETRIS in combination with Opdivo (nivolumab) for
relapsed/refractory Hodgkin lymphoma.
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 injection for intravenous infusion has received FDA
approval for four indications: (1) regular approval for adult
patients with primary cutaneous anaplastic large cell lymphoma
(pcALCL) or CD30-expressing mycosis fungoides (MF) who have
received prior systemic therapy, (2) regular approval for the
treatment of patients with classical Hodgkin lymphoma 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, (3) regular
approval for the treatment of classical Hodgkin lymphoma patients
at high risk of relapse or progression as post-auto-HSCT
consolidation, and (4) 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 Hodgkin lymphoma and sALCL in 2013, and
non-conditional approval for post-ASCT consolidation treatment of
Hodgkin lymphoma patients at increased risk of relapse or
progression.
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 Hodgkin lymphoma 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.
The European Commission extended the current conditional marketing
authorization of ADCETRIS and approved ADCETRIS for the treatment
of adult patients with CD30-positive Hodgkin lymphoma at increased
risk of relapse or progression following ASCT.
ADCETRIS has received marketing authorization by regulatory
authorities in 70 countries for relapsed or refractory Hodgkin
lymphoma and sALCL. 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.
About Seattle Genetics
Seattle Genetics is an innovative biotechnology company
dedicated to improving the lives of people with cancer through
novel antibody-based therapies. The company’s industry-leading
antibody-drug conjugate (ADC) technology harnesses the targeting
ability of antibodies to deliver cell-killing agents directly to
cancer cells. Seattle Genetics commercializes ADCETRIS®
(brentuximab vedotin) for the treatment of several types of
CD30-expressing lymphomas. The company is also advancing a robust
pipeline of novel therapies for solid tumors and blood-related
cancers designed to address significant unmet medical needs and
improve treatment outcomes for patients. More information can be
found at www.seattlegenetics.com and follow @SeattleGenetics on
Twitter.
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 ADCETRIS-treated patients.
ContraindicationADCETRIS concomitant with bleomycin due
to pulmonary toxicity (e.g., interstitial infiltration and/or
inflammation).
Warnings and Precautions
- Peripheral neuropathy (PN):
ADCETRIS causes PN that is predominantly sensory. Cases of motor PN
have also been reported. ADCETRIS-induced PN is cumulative. Monitor
for symptoms such as hypoesthesia, hyperesthesia, paresthesia,
discomfort, a burning sensation, neuropathic pain, or weakness.
Institute dose modifications accordingly.
- Anaphylaxis and infusion
reactions: Infusion-related reactions (IRR), including
anaphylaxis have occurred with ADCETRIS. Monitor patients during
infusion. If an IRR occurs, interrupt the infusion and institute
appropriate medical management. If anaphylaxis occurs, immediately
and permanently discontinue the infusion and administer appropriate
medical therapy. Premedicate patients with a prior IRR before
subsequent infusions. Premedication may include acetaminophen, an
antihistamine, and a corticosteroid.
- 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 ADCETRIS dose. 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
subsequent doses.
- Serious infections and opportunistic
infections: Infections such as pneumonia, bacteremia, and
sepsis or septic shock (including fatal outcomes) have been
reported in ADCETRIS-treated patients. Closely monitor patients
during treatment for 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
use in patients with severe renal impairment.
- 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 use in patients with moderate or
severe hepatic impairment.
- Hepatotoxicity: Serious cases,
including fatal outcomes, have occurred in ADCETRIS-treated
patients. Cases were consistent with hepatocellular injury,
including elevations of transaminases and/or bilirubin, and
occurred after the first ADCETRIS dose or rechallenge. Preexisting
liver disease, elevated baseline liver enzymes, and concomitant
medications may increase the risk. Monitor liver enzymes and
bilirubin. Patients with new, worsening, or recurrent
hepatotoxicity may require a delay, change in dose, or
discontinuation of ADCETRIS.
- 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. Other possible contributory factors
other than ADCETRIS include prior therapies and underlying disease
that may cause immunosuppression. Consider PML diagnosis in
patients 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:
Noninfectious pulmonary toxicity events including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome,
some with fatal outcomes, have been reported. Monitor patients for
signs and symptoms, 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.
- Gastrointestinal (GI)
complications: Acute pancreatitis, including fatal outcomes,
has been reported in ADCETRIS-treated patients. Other fatal and
serious GI complications, including perforation, hemorrhage,
erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic
colitis, and ileus have been reported in ADCETRIS-treated patients.
Lymphoma with preexisting GI involvement may increase the risk of
perforation. In the event of new or worsening GI symptoms, perform
a prompt diagnostic evaluation and treat appropriately.
- Embryo-fetal toxicity: Based on
the mechanism of action and animal studies, ADCETRIS can cause
fetal harm. Advise females of reproductive potential of the
potential risk to the fetus, and to avoid pregnancy during ADCETRIS
treatment and for at least 6 months after the final dose of
ADCETRIS.
Most Common (≥20%) Adverse Reactions: peripheral sensory
neuropathy, fatigue, nausea, diarrhea, neutropenia, upper
respiratory tract infection, and pyrexia.
Drug InteractionsConcomitant 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 PopulationsModerate or severe hepatic
impairment or severe renal impairment: MMAE exposure and adverse
reactions are increased. Avoid use.Advise males with female sexual
partners of reproductive potential to use effective contraception
during, and for at least 6 months after the final dose of ADCETRIS
treatment.
Advise patients to report pregnancy immediately and avoid
breastfeeding while receiving ADCETRIS.
For additional Important Safety Information, including BOXED
WARNING, please see the full Prescribing Information for ADCETRIS
at www.seattlegenetics.com or
www.ADCETRIS.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 potential of ADCETRIS
(brentuximab vedotin) and possible use and benefits from its use,
and anticipated regulatory approval from the FDA and other
regulatory authorities for frontline Hodgkin lymphoma in the
possible time frame and for the possible uses stated above. 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 possibility that the safety
and/or efficacy results of the ECHELON-1 trial in 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 approval for such
submission will be refused or delayed or conditioned or that the
approved uses will be narrower in scope than stated above. In
addition, our regulatory plans may change as a result of
consultation with the FDA or other regulatory authorities. More
information about the risks and uncertainties faced by Seattle
Genetics is contained under the caption “Risk Factors” included in
the company’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2017 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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version on businesswire.com: http://www.businesswire.com/news/home/20180102005172/en/
Seattle Genetics, Inc.Investors:Peggy Pinkston,
425-527-4160ppinkston@seagen.comorMedia:Tricia Larson,
425-527-4180tlarson@seagen.com
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