– Update based on statistically significant 41%
reduction in risk of death vs. previous standard of care in
patients with frontline advanced classical Hodgkin lymphoma –
– First and only targeted therapy inclusive
regimen to improve overall survival in this setting –
Seagen Inc. (NASDAQ: SGEN) today announced an update to the U.S.
Prescribing Information (PI) for ADCETRIS® (brentuximab vedotin) to
include six-year overall survival results from the phase 3
ECHELON-1 clinical trial of ADCETRIS plus combination chemotherapy
in patients with previously untreated Stage III or IV classical
Hodgkin lymphoma compared to chemotherapy alone. The statistically
significant data were presented last year at the annual meetings of
the American Society of Clinical Oncology and the European
Hematology Association.
ADCETRIS was approved for advanced Hodgkin lymphoma in 2018
based on an improvement in progression-free survival in combination
with chemotherapy agents AVD (Adriamycin [doxorubicin], vinblastine
and dacarbazine) in the ECHELON-1 trial. Since its first approval
in 2011, more than 113,000 patients have received ADCETRIS
worldwide.
“The ultimate goal in cancer research is to offer the best
chance for a cure. Patients with advanced classical Hodgkin
lymphoma are often young adults with their whole lives ahead of
them,” said David Epstein, Chief Executive Officer, Seagen. “The
overall survival data are a major step forward in cancer research,
and the transformative benefit offered by the ADCETRIS regimen can
profoundly impact the lives of these patients.”
At a median follow up of approximately six years (73 months) in
the ECHELON-1 study, the ADCETRIS combination with AVD resulted in
a statistically significant 41% reduction in risk of death versus
previous standard of care chemotherapy agents ABVD (Adriamycin
[doxorubicin], bleomycin, vinblastine, and dacarbazine) (hazard
ratio [HR] 0.59; 95% confidence interval [CI]: 0.396, 0.879)
(p-value = 0.009). National treatment guidelines last year
designated ADCETRIS in combination with AVD as a preferred standard
of care for the disease based on the overall survival data.i
Also included in the revised PI are updated data for peripheral
neuropathy at about six years. Among patients who experienced
peripheral neuropathy, 72% had complete resolution, 14% had partial
improvement, and 14% had no improvement. The median time to partial
improvement was 2.9 months (range <1–50), and the median time to
complete resolution was 6.6 months (range <1–67). Of the
patients with ongoing neuropathy (28%), 57% had Grade 1, 30% had
Grade 2, 12% had Grade 3, and <1% had Grade 4 neuropathy. The
safety profile of ADCETRIS in the ECHELON-1 trial was consistent
with previous studies, and no new safety signals were observed.
Please see Important Safety Information, including a
BOXED WARNING for progressive multifocal
leukoencephalopathy (PML), for ADCETRIS below.
About the ECHELON-1 Trial
The ECHELON-1 trial compared ADCETRIS plus AVD to chemotherapy
agents ABVD in 1,334 patients with previously untreated Stage III
or IV classic Hodgkin lymphoma. The trial’s primary endpoint was
modified progression-free survival (PFS) per independent review
facility (IRF). A key secondary endpoint was overall survival,
which was an event-driven, pre-specified, alpha-controlled analysis
in the intention-to-treat population.
The combination of ADCETRIS plus AVD resulted in a statistically
significant 41% reduction in risk of death vs. ABVD (hazard ratio
[HR] 0.59; 95% confidence interval [CI]: 0.396, 0.879) (p-value =
0.009) with overall survival rates of 93.9% for ADCETRIS plus AVD
(95% CI: 91.6, 95.5) vs. 89.4% for ABVD (95% CI: 86.6, 91.7).
Six-year PFS was 82.3% for ADCETRIS plus AVD (95% CI: 79.1, 85.0)
vs. 74.5% for ABVD (95% CI: 70.8, 77.7).
The ADCETRIS plus AVD combination resulted in a manageable
safety profile consistent with prior reports. Treatment-emergent
peripheral neuropathy continued to resolve or improve in both arms,
with 86% (379/443) and 87% (249/286) of patients in the ADCETRIS
plus AVD and ABVD arms, respectively, either completely resolving
(72% vs. 79%) or improving (14% vs. 8%). Fewer patients reported
second malignancies in the ADCETRIS plus AVD arm vs. ABVD (23 vs.
32).
About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate
in the lymphatic system affecting a type of white blood cell called
lymphocytes. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is
distinguished by the presence of Reed-Sternberg cells that usually
have a protein called CD30 on their surface. Approximately 8,830
cases of classic Hodgkin lymphoma will be diagnosed in the United
States during 2023 and 900 people will die from the disease.ii
About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) comprising an
anti-CD30 monoclonal antibody attached by a protease-cleavable
linker to a microtubule disrupting agent, monomethyl auristatin E
(MMAE), utilizing Seagen's 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-positive tumor
cells.
ADCETRIS is approved across seven indications in the U.S.:
- Adult patients with previously untreated Stage III/IV cHL in
combination with doxorubicin, vinblastine, and dacarbazine.
(2018)
- Pediatric patients 2 years and older with previously untreated
high risk cHL in combination with doxorubicin, vincristine,
etoposide, prednisone and cyclophosphamide. (2022)
- Adult patients with cHL at high risk of relapse or progression
as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation. (2015)
- Adult patients with cHL after failure of auto-HSCT or after
failure of at least two prior multi-agent chemotherapy regimens in
patients who are not auto-HSCT candidates. (2011)
- Adult patients with 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. (2018)
- Adult patients with sALCL after failure of at least one prior
multi-agent chemotherapy regimen. (2011)
- Adult patients with primary cutaneous anaplastic large cell
lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who
have received prior systemic therapy. (2017)
ADCETRIS has marketing authorization in more than 70 countries
for relapsed or refractory Hodgkin lymphoma and systemic anaplastic
large cell lymphoma.
Seagen and Takeda jointly develop ADCETRIS. Under the terms of
the collaboration agreement, Seagen has U.S. and Canadian
commercialization rights and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seagen 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.
ADCETRIS® (brentuximab vedotin) for injection 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
Contraindicated with concomitant 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. Patients experiencing new
or worsening PN may require a delay, change in dose, or
discontinuation of ADCETRIS.
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
adult patients who receive ADCETRIS in combination with
chemotherapy for previously untreated Stage III/IV cHL or
previously untreated PTCL, and pediatric patients who receive
ADCETRIS in combination with chemotherapy for previously untreated
high risk cHL.
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 infections.
Tumor lysis syndrome: Patients with rapidly proliferating
tumor and high tumor burden may be at increased risk. Monitor
closely and take appropriate measures.
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. 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. 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
have been reported in ADCETRIS-treated patients. First onset of
symptoms occurred at various times from initiation of ADCETRIS,
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 pre-existing 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 pre-existing 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 anti-hyperglycemic 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 this potential risk, and to use
effective contraception during ADCETRIS treatment and for 2 months
after the last dose of ADCETRIS. Advise male patients with female
partners of reproductive potential to use effective contraception
during ADCETRIS treatment and for 4 months after the last dose of
ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥20% in any study) are
peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia,
upper respiratory tract infection, pyrexia, constipation, vomiting,
alopecia, decreased weight, abdominal pain, anemia, stomatitis,
lymphopenia, mucositis, thrombocytopenia, and febrile
neutropenia.
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to
affect the exposure to monomethyl auristatin E (MMAE). Closely
monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during
ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here.
About Seagen
Founded 25 years ago, Seagen Inc. is a global biotechnology
company that discovers, develops, manufactures and commercializes
targeted cancer therapeutics, with antibody-drug conjugates (ADCs)
at our core. Our colleagues work together with urgency to improve
and extend the lives of people living with cancer. An ADC
technology trailblazer, approximately one-third of FDA-approved and
marketed ADCs use Seagen technology. Seagen is headquartered in
Bothell, Washington and has locations in California, Canada,
Switzerland and across Europe. For additional information, visit
www.seagen.com and follow us on Twitter and LinkedIn.
Forward-Looking Statements
Certain statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS, its safety, efficacy and therapeutic uses.
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 without limitation the
level of utilization and adoption of the referenced 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 or safety signals, and the possibility of adverse regulatory
actions. More information about the risks and uncertainties faced
by Seagen is contained under the caption “Risk Factors” included in
Seagen’s Quarterly Report on Form 10-Q for the quarter ended March
31, 2023, and Seagen’s subsequent reports, filed with the
Securities and Exchange Commission. Seagen 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 applicable law.
____________________
i
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439
ii
https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html
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version on businesswire.com: https://www.businesswire.com/news/home/20230614854786/en/
For Media David Caouette (310) 430-3476 dcaouette@seagen.com For
Investors Doug Maffei (425) 527-4160 dmaffei@seagen.com
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