-Submission of Supplemental Biologics License
Application for ADCETRIS in CD30-Expressing CTCL Planned in First
Half of 2017-
-Positive Phase 3 ALCANZA Trial Data Evaluating
ADCETRIS in CTCL to be Highlighted in Oral Presentation at Upcoming
American Society of Hematology Annual Meeting-
Seattle Genetics, Inc. (Nasdaq: SGEN), a global biotechnology
company, today announced that the U.S. Food and Drug Administration
(FDA) has granted Breakthrough Therapy Designation to ADCETRIS
(brentuximab vedotin) for the treatment of patients with
CD30-expressing mycosis fungoides (MF) and primary cutaneous
anaplastic large cell lymphoma (pcALCL) who require systemic
therapy and have received one prior systemic therapy. MF and pcALCL
are the most common subtypes of cutaneous T-cell lymphoma (CTCL),
accounting for more than 75 percent of the disease. ADCETRIS has
been evaluated in CD30-expressing CTCL in investigator- and
corporate-sponsored clinical trials, including the phase 3 ALCANZA
study. The positive topline results of the ALCANZA trial were
announced in August 2016 and an abstract was accepted for oral
presentation at the upcoming American Society of Hematology (ASH)
annual meeting, December 3-6, 2016 in San Diego, California.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 which
is expressed on skin lesions in approximately 50 percent of
patients with CTCL. ADCETRIS is currently not approved for the
treatment of CTCL.
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 on one or more clinically significant endpoints.
“The decision by the FDA to grant ADCETRIS Breakthrough Therapy
Designation further reinforces our belief that ADCETRIS represents
a meaningful advance in the treatment of CD30-expressing CTCL,”
said Clay Siegall, Ph.D., President and Chief Executive Officer of
Seattle Genetics. “The Breakthrough Therapy Designation supports
our goal to expedite the review and approval process to make
ADCETRIS available to patients in this setting who may benefit. We
look forward to presenting the data from our phase 3 ALCANZA trial
in an oral session at the upcoming ASH annual meeting and intend to
submit a supplemental Biologics License Application to the FDA in
the first half of 2017 for approval in this setting.”
This Breakthrough Therapy Designation was based on data from the
phase 3 ALCANZA clinical trial. The phase 3 ALCANZA trial evaluated
ADCETRIS in CD30-expressing CTCL and met its primary endpoint,
demonstrating a highly statistically significant improvement in the
rate of objective response lasting at least four months (ORR4).
This randomized trial, which received a Special Protocol Assessment
(SPA) agreement from the FDA and scientific advice from the
European Medicines Agency (EMA), compared the use of single-agent
ADCETRIS to a control arm of investigator’s choice of standard
therapies, methotrexate or bexarotene, in 131 patients with
CD30-expressing CTCL who received prior systemic or radiation
therapy.
The title of the phase 3 ALCANZA abstract accepted for oral
presentation at the ASH Annual Meeting is below and can be found at
www.hematology.org:
- Brentuximab Vedotin Demonstrates
Significantly Superior Clinical Outcomes in Patients with
CD30-Expressing Cutaneous T Cell Lymphoma Versus Physician's Choice
(Methotrexate or Bexarotene): the Phase 3 ALCANZA Study (Abstract
#182, oral presentation on Saturday, December 3, 2016 at 2:15 p.m.
PT)
Phase 3 ALCANZA Clinical Trial Design
The ALCANZA trial is a randomized, open-label phase 3 study
designed to evaluate single-agent ADCETRIS versus a control arm of
investigator’s choice of standard therapies, methotrexate or
bexarotene, in patients with CD30-expressing CTCL, including those
with pcALCL or MF. The primary endpoint is ORR4 as assessed by
Global Response Score in the ADCETRIS arm compared to the control
arm. Key secondary endpoints are complete response rate,
progression-free survival and reduction in the burden of symptoms
during treatment. The clinical trial enrolled 131 patients at 50
sites globally. Patients with pcALCL must have received at least
one prior systemic or radiation therapy and patients with MF must
have received at least one prior systemic therapy. Patients
received ADCETRIS every three weeks versus investigator’s choice
for up to approximately one year. This international multi-center
trial has been conducted in North and South America, Europe and
Australia under operational responsibility of Takeda
Pharmaceuticals.
ADCETRIS received orphan drug designation from the FDA for the
treatment of MF, which is the most common type of CTCL. ADCETRIS
also received orphan drug designation from the European Commission
for CTCL, including subtypes pcALCL and MF.
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. Progression from limited
skin involvement may be accompanied by tumor formation, ulceration
and exfoliation, complicated by itching and infections. Advanced
stages are defined by involvement of lymph nodes, peripheral blood
and internal organs. According to published literature, CD30 is
expressed on skin lesions in approximately 50 percent of CTCL
patients.
The standard treatment for systemically pretreated CTCL includes
skin-directed therapies, radiation and systemic therapies. The
systemic therapies currently approved for treatment have
demonstrated 30 to 45 percent objective response rates, with low
complete response rates.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 ongoing
clinical trials, including two phase 3 studies, ECHELON-1 in
frontline classical Hodgkin lymphoma and ECHELON-2 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 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, (2) regular
approval for the treatment of classical Hodgkin lymphoma 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 Hodgkin
lymphoma 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 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.
ADCETRIS has received marketing authorization by regulatory
authorities in 65 countries.
In June 2016, the European Commission extended the current
conditional approval 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. 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 that
develops and commercializes novel antibody-based therapies for the
treatment of cancer. 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.
ADCETRIS® (brentuximab vedotin), the company’s lead product, in
collaboration with Takeda Pharmaceutical Company Limited, is the
first in a new class of ADCs commercially available globally in 65
countries for relapsed classical Hodgkin lymphoma and relapsed
systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics
is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in
a phase 3 trial for acute myeloid leukemia. Headquartered in
Bothell, Washington, Seattle Genetics has a robust pipeline of
innovative therapies for blood-related cancers and solid tumors
designed to address significant unmet medical needs and improve
treatment outcomes for patients. The company has collaborations for
its proprietary ADC technology with a number of companies including
AbbVie, Astellas, Bayer, Genentech, GlaxoSmithKline and Pfizer.
More information can be found at www.seattlegenetics.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
ADCETRIS is contraindicated with concomitant bleomycin due to
pulmonary toxicity (e.g., interstitial infiltration and/or
inflammation).
Warnings and Precautions
- Peripheral neuropathy (PN): ADCETRIS
treatment causes a PN that is predominantly sensory. Cases of motor
PN have also been reported. ADCETRIS-induced PN 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.
- 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. Patients who experienced a prior
infusion-related reaction should be premedicated for 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
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 subsequent doses.
- 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 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 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.
- Gastrointestinal (GI) complications:
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 findings in animals, ADCETRIS can cause
fetal harm when administered to a pregnant woman. Females of
reproductive potential should avoid pregnancy during ADCETRIS
treatment and for at least 6 months after the final dose of
ADCETRIS.
Adverse Reactions
In two uncontrolled single-arm trials of ADCETRIS as monotherapy
in 160 patients with relapsed classical HL and sALCL, 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.
In a placebo-controlled trial of ADCETRIS in 329 patients with
classical HL at high risk of relapse or progression post-auto-HSCT,
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.
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
MMAE exposure and adverse reactions are increased in patients
with moderate or severe hepatic impairment or severe renal
impairment. Avoid use.
Advise females of reproductive potential to avoid pregnancy
during ADCETRIS treatment and for at least 6 months after the final
dose of ADCETRIS.
Advise males with female sexual partners of reproductive
potential to use effective contraception during ADCETRIS treatment
and for at least 6 months after the final dose of ADCETRIS.
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
and commercial potential of ADCETRIS, including ADCETRIS’ potential
as a treatment for CTCL, the anticipated benefits of Seattle
Genetics’ ADCETRIS clinical development program, and the potential
submission of applications (e.g., a supplemental Biologics License
Application in the U.S.) seeking label expansion for ADCETRIS use
in the CTCL 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, the
possibility that data from the ALCANZA study may not be deemed
sufficient by regulatory agencies to support approval of ADCETRIS
for use in the CTCL setting, and adverse regulatory actions
affecting ADCETRIS, all of which could result in Seattle Genetics
being unable to expand ADCETRIS’ labeled indications of use for
CTCL or any other settings. Seattle Genetics may also experience
delays in submission or review of its supplemental Biologics
License, in each case for a variety of reasons, including the
inherent difficulty and uncertainty of pharmaceutical product
development or 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, 2016 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/20161110005421/en/
Seattle Genetics, Inc.Investors:Peggy Pinkston,
425-527-4160ppinkston@seagen.comorMedia:Tricia Larson,
425-527-4180tlarson@seagen.com
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