- Approval of Supplemental New Drug Submission
for ADCETRIS in Combination with CHP Chemotherapy in Frontline
CD30-Expressing Peripheral T-Cell Lymphoma based on Positive Phase
3 ECHELON-2 Clinical Trial Results -
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that Health
Canada has approved the supplemental New Drug Submission that
expands the use of ADCETRIS (brentuximab vedotin) in combination
with CHP (cyclophosphamide, doxorubicin, prednisone) chemotherapy
for the treatment of previously untreated adult patients with
systemic anaplastic large cell lymphoma (sALCL), peripheral T-cell
lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic
T-cell lymphoma (AITL), whose tumours express CD30. The approval is
based on positive results of the phase 3 ECHELON-2 clinical trial
that compared ADCETRIS plus CHP to CHOP (cyclophosphamide,
doxorubicin, vincristine, prednisone). Health Canada granted a
Priority Review Designation for this submission. ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30, which is expressed
on the surface of several types of PTCL.
“The Health Canada approval of ADCETRIS (brentuximab vedotin) in
combination with CHP chemotherapy in newly diagnosed
CD30-expressing peripheral T-cell lymphoma represents the first
major advance for Canadian patients with PTCL in decades,” said
Kerry Savage, M.D., Medical Oncologist at the BC Cancer Agency,
Professor of Medicine at the University of British Columbia and
investigator on the ECHELON-2 clinical trial. “The approval is
based on the ECHELON-2 clinical trial that demonstrated ADCETRIS
(brentuximab vedotin) plus CHP regimen was superior for both
progression-free survival and all key secondary endpoints,
including overall survival, when compared to the standard of care
CHOP chemotherapy.”
“The current standard of care for initial treatment of
peripheral T-cell lymphoma is multi-agent chemotherapy, which
results in low complete remission rates and poor progression-free
and overall survival. ECHELON-2 is the first randomized trial to
demonstrate an overall survival benefit over established standard
therapy, making it a meaningful advance in the treatment of these
rare lymphomas,” said Roger Dansey, M.D., Chief Medical Officer at
Seattle Genetics. “With this new indication for ADCETRIS,
physicians and eligible patients in Canada now have access to this
important new regimen for treating frontline CD30-expressing
peripheral T-cell lymphoma, another milestone supporting our plans
to continue to expand ADCETRIS globally to patients in need.”
In May 2019, Health Canada approved the supplemental New Drug
Submission that expanded the use of ADCETRIS in combination with
AVD (Adriamycin, vinblastine and dacarbazine) chemotherapy in
patients with previously untreated Stage IV Hodgkin lymphoma (HL)
based on the results of the phase 3 ECHELON-1 clinical trial.
About T-Cell Lymphomas
There are more than 60 subtypes of non-Hodgkin lymphomas which
are broadly divided into two major groups: B-cell lymphomas, which
develop from abnormal B-lymphocytes, and T-cell lymphomas, which
develop from abnormal T-lymphocytes. There are many different forms
of T-cell lymphomas, some of which are extremely rare. T-cell
lymphomas can be aggressive (fast-growing) or indolent
(slow-growing). PTCL accounts for approximately 10 percent of
non-Hodgkin lymphoma cases in the U.S. and Europe and may be as
high as 24 percent in parts of Asia.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical
trials in CD30-expressing lymphomas. These include three completed
phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell
lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and
ALCANZA in cutaneous T-cell 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 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 in 2013
for patients with (1) HL after failure of autologous stem cell
transplant (ASCT) or after failure of at least two multi-agent
chemotherapy regimens in patients who are not ASCT candidates and
(2) sALCL after failure of at least one multi-agent chemotherapy
regimen. Non-conditional approval was granted for (3) post-ASCT
consolidation treatment of patients with HL at increased risk of
relapse or progression in 2017, (4) adult patients with pcALCL or
CD30-expressing MF who have received prior systemic therapy in
2018, (5) for previously untreated patients with Stage IV HL in
combination with doxorubicin, vinblastine, and dacarbazine in 2019,
and (6) for previously untreated adult patients with sALCL,
peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or
angioimmunoblastic T-cell lymphoma (AITL), whose tumors express
CD30, in combination with cyclophosphamide, doxorubicin, prednisone
in 2019.
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) for 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, (4) for
the treatment of adult patients with CD30-positive cutaneous T-cell
lymphoma (CTCL) after at least one prior systemic therapy and (5)
for the treatment of adult patients with previously untreated
CD30-positive Stage IV Hodgkin lymphoma in combination with AVD
(Adriamycin®, vinblastine and dacarbazine).
ADCETRIS has received marketing authorization by regulatory
authorities in 73 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 a late-stage pipeline including enfortumab vedotin for
metastatic urothelial cancer, currently being reviewed for approval
by the FDA, and tisotumab vedotin in clinical trials for metastatic
cervical cancer, which utilize our proprietary ADC technology. In
addition, tucatinib, a small molecule tyrosine kinase inhibitor, is
in late-stage development for HER2-positive metastatic breast
cancer and in clinical development for metastatic colorectal
cancer. We are also 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. 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: 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 beginning with Cycle 1 for patients who receive
ADCETRIS in combination with chemotherapy for previously untreated
Stage III/IV cHL 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
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: 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. In addition to ADCETRIS therapy, other possible
contributory factors 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: 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, including severe abdominal pain, perform a prompt
diagnostic evaluation and treat appropriately.
- Hyperglycemia: Serious cases, such as new-onset
hyperglycemia, exacerbation of preexisting diabetes mellitus, and
ketoacidosis (including fatal outcomes) have been reported with
ADCETRIS. Hyperglycemia occurred more frequently in patients with
high body mass index or diabetes. Monitor serum glucose and if
hyperglycemia develops, administer antihyperglycemic medications as
clinically indicated.
- 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.
Drug Interactions
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.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here.
Forward-Looking Statements
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the potential
utilization of ADCETRIS (brentuximab vedotin) for previously
untreated adult patients with systemic anaplastic large cell
lymphoma, peripheral T-cell lymphoma-not otherwise specified or
angioimmunoblastic T-cell lymphoma, whose tumours express CD30 in
Canada and the therapeutic potential of ADCETRIS in this
indication. 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, 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,
2019 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20191125005237/en/
Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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