Approval Based on Positive Phase 3 ALCANZA
Trial Results, which Demonstrated a Highly Statistically
Significant Improvement in Rate of Objective Response Lasting at
Least Four Months, Median Progression-Free Survival, and
Improvement in Symptom Burden in ADCETRIS Arm
Seattle Genetics, Inc. (Nasdaq: SGEN) reported today that its
collaborator, Takeda Pharmaceutical Company Limited, announced that
the European Commission has extended the current conditional
marketing authorization for ADCETRIS (brentuximab vedotin) to
include the treatment of adult patients with CD30-positive
cutaneous T-cell lymphoma (CTCL) after at least one prior systemic
therapy. ADCETRIS is an antibody-drug conjugate (ADC) directed to
CD30, which is expressed on the surface of Hodgkin lymphoma cells
and several types of non-Hodgkin lymphoma, including CTCL. The
decision follows a positive opinion from the Committee for
Medicinal Products for Human Use (CHMP) on November 9, 2017.
“CTCL is a debilitating and disfiguring disease with few
effective and durable treatment options,” said Clay Siegall, Ph.D.,
President and Chief Executive Officer at Seattle Genetics. “The
approval of ADCETRIS for use in the European Union in CD30-positive
CTCL patients represents a meaningful advance for patients with
CTCL. We are pleased that our partner Takeda is able to make this
therapeutic option available to patients in Europe. Since ADCETRIS
was first approved by the FDA in 2011, Seattle Genetics and Takeda
have made significant progress in our goal to establish ADCETRIS as
the foundation of care for CD30-expressing lymphomas, and we are
working together on our next milestone of securing FDA approval and
European Union marketing authorization for ADCETRIS’ use as a
treatment for frontline advanced Hodgkin lymphoma.”
The marketing authorization for ADCETRIS is valid in 28
countries of the European Union (EU), Norway, Liechtenstein and
Iceland. It is based on positive results from a phase 3 trial
called ALCANZA that were presented at the 58th American Society of
Hematology (ASH) annual meeting in December 2016, published online
in the Lancet in June 2017, and recently updated in a poster
presentation at the 59th ASH annual meeting in December 2017. The
trial achieved its primary endpoint with the ADCETRIS treatment arm
demonstrating a highly statistically significant improvement in the
rate of objective response lasting at least four months (ORR4)
versus the control arm as assessed by an independent review
facility. The ORR4 was 56.3 percent in the ADCETRIS arm compared to
12.5 percent in the control arm (p-value <0.001). The key
secondary endpoints specified in the protocol, including complete
response rate, progression-free survival and reduction in skin
symptom burden as measured by the Skindex-29 questionnaire, were
all highly statistically significant in favor of the ADCETRIS arm.
The safety profile associated with ADCETRIS from the ALCANZA trial
was generally consistent with the existing prescribing information.
The most common adverse events of any grade include: anemia,
peripheral sensory neuropathy, nausea, diarrhea, fatigue and
neutropenia.
For further details about the European Commission decision,
please visit the European Medicines Agency website:
www.ema.europa.eu/ema.
In November 2017, the U.S. Food and Drug Administration (FDA)
approved ADCETRIS for the treatment of adult patients with primary
cutaneous anaplastic large cell lymphoma (pcALCL) or
CD30-expressing mycosis fungoides (MF) who have received prior
systemic therapy based on the results of the phase 3 ALCANZA
clinical trial. Together, pcALCL and CD30-expressing MF comprise
approximately 70 percent of CTCL diagnoses and the majority of
patients who require systemic therapy. ADCETRIS is currently not
approved as a frontline therapy for Hodgkin lymphoma.
About CTCL
Lymphoma 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. Cutaneous
lymphomas are a category of non-Hodgkin lymphoma that primarily
involve the skin. According to the Cutaneous Lymphoma Foundation,
CTCL is the most common type of cutaneous lymphoma and typically
presents with red, scaly patches or thickened plaques of skin that
often mimic eczema or chronic dermatitis. The most common subtypes
of CTCL include mycosis fungoides and primary cutaneous anaplastic
large cell lymphoma. Progression from limited skin involvement may
be accompanied by skin tumor formation, ulceration and exfoliation,
complicated by itching and infections. Advanced stages are defined
by involvement of lymph nodes, peripheral blood and internal
organs. The standard treatment for CTCL patients includes
skin-directed therapies, radiation and systemic therapies. Prior to
the FDA approval of ADCETRIS, systemic therapies approved for
treatment demonstrated 30 to 45 percent objective response rates,
with low complete response rates.
About ADCETRIS
ADCETRIS 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 received conditional marketing authorization from the
European Commission for four 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, (2) the treatment of adult
patients with relapsed or refractory sALCL, (3) for the treatment
of adult patients with CD30-positive Hodgkin lymphoma at increased
risk of relapse or progression following ASCT, and (4) for the
treatment of adult patients with CD30-positive cutaneous T-cell
lymphoma (CTCL) after at least one prior systemic therapy.
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.
Contraindication
ADCETRIS 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 Interactions
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
Moderate 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) for uses for which
ADCETRIS has not received regulatory approval such as frontline
Hodgkin lymphoma, and our goal to establish ADCETRIS as the
foundation of care in CD30-expressing lymphomas. 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 our 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. In addition, we may be unable to show
sufficient activity for other uses that have not received
regulatory approval, and ADCETRIS may be subject to the possible
risk of additional adverse events and adverse regulatory action.
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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20180122005233/en/
Seattle Genetics, Inc.Investors:Peggy Pinkston,
425-527-4160ppinkston@seagen.comorMedia:Tricia Larson,
425-527-4180tlarson@seagen.com
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