BOTHELL, Wash.–(BUSINESS WIRE)–Seattle
Genetics, Inc. (Nasdaq:SGEN) today announced that its collaborator,
Takeda Pharmaceutical Company Limited, received approval from the
European Commission to extend the marketing authorization for ADCETRIS
(brentuximab vedotin) to include ADCETRIS in combination with AVD
(Adriamycin®, vinblastine and dacarbazine) in adults patients
with previously untreated CD30+ stage IV classical Hodgkin lymphoma
(HL). The decision follows a positive opinion from the Committee for
Medicinal Products for Human Use (CHMP) on December 13, 2018. As a
result, Seattle Genetics will receive a milestone payment from Takeda of
$30 million. ADCETRIS is an antibody-drug conjugate (ADC) directed to
CD30, a defining marker of classical HL that plays a role in tumor
growth and survival.
“Receipt of this milestone payment reflects continued progress by our
partner Takeda to expand ADCETRIS approved indications globally,” said
Clay Siegall, Ph.D., President and Chief Executive Officer at Seattle
Genetics. “We look forward to continuing our work with Takeda to
establish ADCETRIS as the global foundation of care for CD30-expressing
lymphomas, including Hodgkin lymphoma.”
The marketing authorization for ADCETRIS is based on positive results
from the ECHELON-1 phase 3 clinical trial that were presented in the
Plenary Scientific Session at the 59th American Society of
Hematology (ASH) annual meeting in December 2017 with simultaneous
publication in the New England Journal of Medicine.
In September 2018, the Japanese Ministry of Health, Labour and Welfare
approved ADCETRIS in combination with AVD as a frontline treatment
option for CD30-positive HL patients in Japan. In March 2018, the U.S.
Food and Drug Administration (FDA) approved ADCETRIS in combination with
AVD for the treatment of adult patients with previously untreated stage
III or IV classical HL based on the positive results of the ECHELON-1
phase 3 clinical trial.
For more information about the European Commission decision, please
visit the European Medicines Agency website: www.ema.europa.eu/ema.
About Classical 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 in
CD30-expressing lymphomas. These include three completed phase 3 trials:
ECHELON-2 in frontline peripheral T-cell lymphomas, ECHELON-1 in
previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell
lymphoma. The phase 3 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 for injection for intravenous infusion has received FDA
approval for six indications in adult patients with: (1) previously
untreated systemic anaplastic large cell lymphoma (sALCL) or other
CD30-expressing peripheral T-cell lymphomas (PTCL), including
angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in
combination with cyclophosphamide, doxorubicin, and prednisone, (2)
previously untreated Stage III or IV classical Hodgkin lymphoma (cHL),
in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL
at high risk of relapse or progression as post-autologous hematopoietic
stem cell transplantation (auto-HSCT) consolidation, (4) 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, (5)
sALCL after failure of at least one prior multi-agent chemotherapy
regimen, and (6) 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 in 2017, and adults with pcALCL or
CD30-expressing MF who have had prior systemic therapy in 2018.
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 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL.
See select important safety information, including Boxed Warning, 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, 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) Important Safety Information
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. Start primary prophylaxis with G-CSF beginning
with Cycle 1 for patients who receive ADCETRIS in combination with
chemotherapy for previously untreated Stage III or IV classical HL or
previously untreated PTCL. Monitor complete blood counts prior to each
ADCETRIS dose. Monitor more frequently 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 ADCETRIS 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
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% in any study) Adverse Reactions: Peripheral
neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory
tract infection, pyrexia, constipation, vomiting, alopecia, decreased
weight, abdominal pain, anemia, stomatitis, lymphopenia and mucositis.
Concomitant use of strong CYP3A4 inhibitors or inducers 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.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the potential benefit
and use of ADCETRIS (brentuximab vedotin), the goal of establishing
ADCETRIS as the global foundation of care for CD30-expressing lymphomas
and the anticipated payment of a milestone payment by Takeda. Actual
results or developments may differ materially from those projected or
implied in these forward-looking statements due to factors such as
utilization and adoption of the approved treatment regimen by
prescribing physicians, competitive conditions including the
availability of alternative treatment regimens, the availability and
extent of reimbursement, the risk of adverse events, adverse regulatory
action and unanticipated delays or other obstacles preventing the timely
receipt of Takeda’s collaboration payments. More information about the
risks and uncertainties faced by Seattle Genetics is contained under the
caption “Risk Factors” included in the company’s Annual Report on Form
10-K for the year ended December 31, 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 otherwise, except as
required by law.