-Approval Triggers Milestone Payment to Seattle Genetics of $10
BOTHELL, Wash.–(BUSINESS WIRE)–Seattle
Genetics, Inc. (Nasdaq: SGEN) today announced that its collaborator,
Takeda Pharmaceutical Company Limited (Takeda), has received approval
from the Japanese Ministry of Health, Labour and Welfare for ADCETRIS
(brentuximab vedotin) in combination with doxorubicin, vinblastine and
dacarbazine (AVD) as a frontline treatment option for CD30-positive
Hodgkin lymphoma patients in Japan. As a result, Seattle Genetics will
receive a milestone payment from Takeda of $10 million. The approval in
Japan was based on the positive outcome from the phase 3 ECHELON-1 trial.
“This approval marks another important milestone in expanding the
ADCETRIS brand globally and redefining the way newly diagnosed Hodgkin
lymphoma patients are treated around the world,” said Clay Siegall,
Ph.D., President and Chief Executive Officer of Seattle Genetics.
“ADCETRIS is approved in 71 countries and generated global sales of
approximately $640 million in 2017, underscoring its progress toward
becoming the foundation of therapy for patients with CD30-expressing
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. Seattle
Genetics is entitled to receive progress- and sales-dependent milestone
payments. In addition, Seattle Genetics receives tiered double-digit
royalties with percentages ranging from the mid-teens to mid-twenties
based on net sales of ADCETRIS within Takeda’s territories.
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: 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. According to the Lymphoma Coalition,
over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each
year and approximately 25,000 people die each year from this cancer.
About ADCETRIS (brentuximab vedotin)
ADCETRIS is being evaluated broadly in more than 70 clinical trials,
including the ongoing phase 3 ECHELON-2 trial in frontline peripheral
T-cell lymphomas (also known as mature T-cell lymphoma), the completed
phase 3 ALCANZA trial in cutaneous T-cell lymphoma (CTCL) and the
completed ECHELON-1 trial in previously untreated Hodgkin lymphoma, as
well as trials in many additional types of CD30-positive 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 injection for intravenous infusion has received FDA approval
for five indications in adult patients with: (1) previously untreated
Stage III or IV classical Hodgkin lymphoma (cHL), in combination with
chemotherapy, (2) cHL at high risk of relapse or progression as
post-autologous hematopoietic stem cell transplantation (auto-HSCT)
consolidation, (3) cHL after failure of auto-HSCT or failure of at least
two prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates, (4) sALCL after failure of at least one prior
multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic
large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF)
who have received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions for relapsed or
refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional
approval for post-autologous stem cell transplantation (ASCT)
consolidation treatment of Hodgkin lymphoma patients at increased risk
of relapse or progression.
ADCETRIS received conditional marketing authorization from the European
Commission in October 2012. The approved indications in Europe are: (1)
for the treatment of adult patients with relapsed or refractory
CD30-positive Hodgkin lymphoma following 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
ADCETRIS has received marketing authorization by regulatory authorities
in 71 countries for relapsed or refractory Hodgkin lymphoma and sALCL.
See select important safety information, including Boxed Warning, below.
About Seattle Genetics
Seattle Genetics, Inc. is an emerging multi-product, global
biotechnology company that develops and commercializes transformative
therapies targeting cancer to make a meaningful difference in people’s
lives. ADCETRIS® (brentuximab vedotin) utilizes the company’s
industry-leading antibody-drug conjugate (ADC) technology and is
currently approved for the treatment of multiple CD30-expressing
lymphomas. Beyond ADCETRIS, the company has established a pipeline of
novel targeted therapies at various stages of clinical testing,
including three in ongoing pivotal trials for solid tumors. Enfortumab
vedotin for metastatic urothelial cancer and tisotumab vedotin for
metastatic cervical cancer utilize our proprietary ADC technology.
Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal
trial for HER2-positive metastatic breast cancer. In addition, we are
leveraging our expertise in empowered antibodies to build a portfolio of
proprietary immuno-oncology agents in clinical trials targeting
hematologic malignancies and solid tumors. The company is headquartered
in Bothell, Washington, and has a European office in Switzerland. For
more information on our robust pipeline, visit www.seattlegenetics.com
and follow @SeattleGenetics on Twitter.
ADCETRIS (brentuximab vedotin) U.S. Select Important Safety
BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML):
JC virus infection resulting in PML and death can occur in
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
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: Fatal and serious cases of febrile
neutropenia have been reported with ADCETRIS. Prolonged (≥1 week)
severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can
occur with ADCETRIS. Administer G-CSF primary prophylaxis starting
with Cycle 1 for previously untreated patients who receive ADCETRIS in
combination with chemotherapy for Stage III or IV HL. 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
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
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: Fatal and serious cases 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: Fatal cases of JC virus infection resulting in PML and
death have 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
Pulmonary toxicity: Fatal and serious events of noninfectious
pulmonary toxicity including pneumonitis, interstitial lung disease,
and acute respiratory distress syndrome 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: Fatal and serious cases of
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
have been reported with ADCETRIS. If SJS or TEN occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
Gastrointestinal (GI) complications: Fatal and serious cases of
acute pancreatitis have been reported. Other fatal and serious GI
complications include perforation, hemorrhage, erosion, ulcer,
intestinal obstruction, enterocolitis, neutropenic colitis, and ileus.
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: Neutropenia, anemia, peripheral
sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting,
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 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
Certain of the statements made in this press release are
forward-looking, such as those, among others, relating to the potential
commercial opportunity for ADCETRIS in Japan and the potential for
approval and commercialization of ADCETRIS in other countries, and the
potential of redefining the treatment of newly diagnosed Hodgkin
lymphoma patients around the world. 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 risks that ADCETRIS will not be widely adopted by physicians in
Japan or reimbursement may be difficult to secure in Japan, or that we
may otherwise encounter challenges in commercializing ADCETRIS in the
jurisdictions in which it has been approved for use in newly diagnosed
Hodgkin lymphoma patients in combination with chemotherapy. In addition,
data from clinical trials may not support marketing approval for
submitted indications in other countries. 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, 2018 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
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160