– Results of pivotal confirmatory trial
found the enfortumab vedotin plus pembrolizumab combination
significantly extended overall survival and progression-free
survival vs standard platinum containing chemotherapy–
– If approved, the combination would be the
first and only antibody-drug conjugate plus PD-1
inhibitor treatment alternative to chemotherapy in this
patient population –
TOKYO and BOTHELL,
Wash., Nov. 30, 2023 /PRNewswire/
-- Astellas Pharma Inc. (TSE:4503, President and CEO:
Naoki Okamura, "Astellas") and
Seagen Inc. (Nasdaq: SGEN) today announced that on November 30, 2023 the U.S. Food and Drug
Administration (FDA) accepted for priority review a supplemental
Biologics License Application (sBLA) for PADCEV®
(enfortumab vedotin-ejfv) with KEYTRUDA®
(pembrolizumab) as a combination therapy for the treatment of adult
patients with locally advanced or metastatic urothelial cancer
(la/mUC), a form of bladder cancer that has spread to surrounding
organs or muscles, or other parts of the body.
Under the Prescription Drug User Fee Act (PDUFA), the FDA has
set a target action date of May 9,
2024. The FDA is reviewing the application under its
Real-Time Oncology Review (RTOR) program, which aims to explore a
more efficient review process to ensure that safe and effective
treatments are available to patients as early as possible. If
approved, this combination would be the first treatment option for
cisplatin eligible and ineligible patients.
In the U.S., it is estimated that 82,290 people will be
diagnosed with bladder cancer in 2023.i Urothelial
cancer accounts for 90% of all bladder cancers and can also be
found in the renal pelvis, ureter and urethra.ii
Approximately 12% of cases are locally advanced or metastatic
urothelial cancer at diagnosis.iii Most la/mUC patients
will progress within nine months and long-term survival rates are
poor.iv
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of
Oncology Development, Astellas
"We look forward to the FDA's
review of this application, which, if approved, will convert the
accelerated approval of the combination based on results from the
EV-103 study to standard approval for all first-line locally
advanced or metastatic urothelial cancer patients, expanding the
indication to cisplatin eligible patients. These patients have a
critical need for innovative new therapies, as chemotherapy has
been the standard of care for over 30 years. We are committed to
delivering on our goal of helping patients with advanced urothelial
cancer live longer."
Roger Dansey, M.D., President,
Research and Development, Seagen
"Through our clinical
development program, data have consistently shown the impact of
combining enfortumab vedotin with pembrolizumab for advanced
bladder cancer. The FDA's acceptance of our application is a
critical step in our work as we seek to deliver this combination to
more patients who currently have few treatment options at the
advanced stage."
The sBLA for first-line use of the combination is based on
results from the Phase 3 EV-302 clinical trial (also known as
KEYNOTE-A39). The study found that the combination improved overall
survival (OS) and progression-free survival (PFS) with
statistically significant and clinically meaningful results in
patients with previously untreated la/mUC compared to
platinum-containing chemotherapy. The safety results were
consistent with those previously reported with this combination,
and no new safety issues were identified.
Please see Important Safety Information at the end of this press
release, including BOXED WARNING for PADCEV (enfortumab
vedotin-ejfv).
In February 2020, PADCEV in
combination with KEYTRUDA was granted Breakthrough Therapy
designation by the FDA and the EV-103 sBLA received Priority Review
designation in December 2022. In
April 2023, the FDA granted
accelerated approval to the combination for the treatment of adult
patients with la/mUC who are not eligible to receive
cisplatin-containing chemotherapy based on tumor response rate and
durability of response from the EV-103 trial. The EV-302 trial,
which is intended to serve as the confirmatory trial for the U.S.
accelerated approval and as the basis for global regulatory
submissions, is also intended to expand the indication into the
cisplatin-eligible patient population.
About EV-302
The EV-302 trial is an open-label,
randomized, controlled Phase 3 study, evaluating enfortumab vedotin
in combination with pembrolizumab versus chemotherapy in patients
with previously untreated la/mUC. The study enrolled 886 patients
with previously untreated la/mUC who were eligible for cisplatin-
or carboplatin-containing chemotherapy regardless of PD-L1 status.
Patients were randomized to receive either enfortumab vedotin in
combination with pembrolizumab, or chemotherapy. The dual primary
endpoints of this trial are OS and PFS per RECIST v1.1 by blinded
independent central review (BICR). Select secondary endpoints
include overall response rate (ORR) and duration of response (DOR)
per RECIST v1.1 by BICR, and safety.
The EV-302 trial is part of an extensive program evaluating this
combination in multiple stages of urothelial cancer and other solid
tumors. Findings from EV-302 were presented at the European
Society for Medical Oncology (ESMO) Congress 2023 in October 2023.
About Bladder and Urothelial Cancer
- Urothelial cancer, or bladder cancer, begins in the urothelial
cells, which line the urethra, bladder, ureters, renal pelvis, and
some other organs.ii
- If bladder cancer has spread to surrounding organs or muscles,
it is called locally advanced disease. If the cancer has spread to
other parts of the body, it is called metastatic
disease. v
- Globally, approximately 573,000 new cases of bladder cancer and
212,000 deaths are reported annually.vi
Ongoing Investigational Trials
The EV-302 trial
(NCT04223856) is an open-label, randomized, controlled Phase 3
study, evaluating the impact of treatment with enfortumab vedotin
in combination with pembrolizumab versus chemotherapy in patients
with previously untreated locally advanced or metastatic urothelial
cancer (la/mUC) who were eligible for cisplatin- or
carboplatin-containing chemotherapy regardless of PD-L1
status.
The EV-103 trial (NCT03288545) is an ongoing,
multi-cohort, open-label, multicenter Phase 1b/2 study investigating
enfortumab vedotin alone or in combination with
pembrolizumab and/or chemotherapy in first- or second-line settings
in patients with la/mUC and in patients with muscle-invasive
bladder cancer (MIBC).
Enfortumab vedotin in combination with pembrolizumab is being
investigated in an extensive program in multiple stages of
urothelial cancer, including two Phase 3 clinical trials in MIBC in
EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303
(NCT03924895, also known as KEYNOTE-905). The use of enfortumab
vedotin in combination with pembrolizumab in MIBC has not been
proven safe or effective.
The EV-202 trial (NCT04225117) is an ongoing, multi-cohort,
open-label, multicenter Phase 2 study investigating enfortumab
vedotin alone in patients with previously treated advanced solid
tumors. This study also has a cohort that is investigating
enfortumab vedotin in combination with pembrolizumab in patients
with previously untreated recurrent/metastatic head and neck
squamous cell carcinoma.
About PADCEV® (enfortumab
vedotin-ejfv)
PADCEV (enfortumab vedotin-ejfv) is a
first-in-class antibody-drug conjugate (ADC) that is directed to
Nectin-4, a protein located on the surface of cells and highly
expressed in bladder
cancer.vii Nonclinical data suggest the
anticancer activity of PADCEV is due to its binding to
Nectin-4-expressing cells, followed by the internalization and
release of the anti-tumor agent monomethyl auristatin E (MMAE) into
the cell, which result in the cell not reproducing (cell cycle
arrest) and in programmed cell death
(apoptosis).viii
PADCEV (enfortumab vedotin-ejfv) U.S. Indication &
Important Safety Information
BOXED WARNING: SERIOUS SKIN REACTIONS
- PADCEV can cause severe and fatal cutaneous adverse reactions
including Stevens-Johnson syndrome
(SJS) and Toxic Epidermal Necrolysis (TEN), which occurred
predominantly during the first cycle of treatment, but may occur
later.
- Closely monitor patients for skin reactions.
- Immediately withhold PADCEV and consider referral for
specialized care for suspected SJS or TEN or severe skin
reactions.
- Permanently discontinue PADCEV in patients with confirmed SJS
or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
Indication
PADCEV®, as a single agent, is
indicated for the treatment of adult patients with locally advanced
or metastatic urothelial cancer (mUC) who:
- have previously received a programmed death receptor-1 (PD-1)
or programmed death-ligand 1 (PD-L1) inhibitor and
platinum-containing chemotherapy, or
- are ineligible for cisplatin-containing chemotherapy and have
previously received one or more prior lines of
therapy.1
PADCEV, in combination with pembrolizumab, is indicated for the
treatment of adult patients with locally advanced or metastatic
urothelial cancer (mUC) who are not eligible for
cisplatin-containing chemotherapy.1
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.
Important Safety Information
Warnings and Precautions
Skin reactions Severe cutaneous adverse reactions,
including fatal cases of SJS or TEN occurred in patients treated
with PADCEV. SJS and TEN occurred predominantly during the first
cycle of treatment but may occur later. Skin reactions occurred in
56% (all grades) of the 753 patients treated with PADCEV as a
single agent in clinical trials. Twenty-four percent (24%) of
patients had maculo-papular rash and 33% had pruritus. Grade 3-4
skin reactions occurred in 12% of patients, including
maculo-papular rash, erythematous rash, rash or drug eruption,
symmetrical drug-related intertriginous and flexural exanthema
(SDRIFE), bullous dermatitis, exfoliative dermatitis, and
palmar-plantar erythrodysesthesia. The median time to onset of
severe skin reactions was 0.7 months (range: 0.1 to 6 months).
Among patients experiencing a skin reaction leading to dose
interruption who then restarted PADCEV (n=59), 24% of patients
restarting at the same dose and 16% of patients restarting at a
reduced dose experienced recurrent severe skin reactions. Skin
reactions led to discontinuation of PADCEV in 2.6% of patients.
When PADCEV was given in combination with pembrolizumab, the
incidence of skin reactions, including severe events, occurred at a
higher rate. Skin reactions occurred in 72% (all grades) of the 121
patients treated with PADCEV in combination with pembrolizumab in
clinical trials. The majority of the skin reactions that occurred
with combination therapy included maculo-papular rash, macular rash
and papular rash. Grade 3-4 skin reactions occurred in 20% of
patients (Grade 3: 19%, Grade 4: 0.8%), including maculo-papular
rash, bullous dermatitis, dermatitis, exfoliative dermatitis,
pemphigoid, rash, erythematous rash, macular rash, and papular
rash. A fatal reaction of bullous dermatitis occurred in one
patient (0.8%). The median time to onset of severe skin reactions
was 2.6 months (range: 0.3 to 16 months). Skin reactions led to
discontinuation of PADCEV in 6% of patients. Monitor patients
closely throughout treatment for skin reactions. Consider topical
corticosteroids and antihistamines, as clinically indicated. For
persistent or recurrent Grade 2 skin reactions, consider
withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for
specialized care for suspected SJS, TEN or for Grade 3 skin
reactions. Permanently discontinue PADCEV in patients with
confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin
reactions.
Hyperglycemia and diabetic ketoacidosis
(DKA). Hyperglycemia and diabetic ketoacidosis (DKA), including
fatal events, occurred in patients with and without pre-existing
diabetes mellitus, treated with PADCEV. Patients with baseline
hemoglobin A1C ≥8% were excluded from clinical trials. In clinical
trials of PADCEV as a single agent, 14% of the 753 patients treated
with PADCEV developed hyperglycemia; 7% of patients developed Grade
3-4 hyperglycemia. Fatal events of hyperglycemia and diabetic
ketoacidosis occurred in one patient each (0.1%). The incidence of
Grade 3-4 hyperglycemia increased consistently in patients with
higher body mass index and in patients with higher baseline A1C.
Five percent (5%) of patients required initiation of insulin
therapy for treatment of hyperglycemia. The median time to onset of
hyperglycemia was 0.6 months (range: 0.1 to 20 months).
Hyperglycemia led to discontinuation of PADCEV in 0.4% of patients.
Closely monitor blood glucose levels in patients with, or at risk
for, diabetes mellitus or hyperglycemia. If blood glucose is
elevated (>250 mg/dL), withhold PADCEV.
Pneumonitis/Interstitial Lung Disease (ILD) Severe,
life-threatening or fatal pneumonitis/ILD occurred in patients
treated with PADCEV. In clinical trials of PADCEV as a single
agent, 2.9% of the 753 patients treated with PADCEV had
pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median
time to onset of pneumonitis/ILD was 2.7 months (range: 0.6 to 6
months). The incidence of pneumonitis/ILD, including severe events
occurred at a higher rate when PADCEV was given in combination with
pembrolizumab. When PADCEV was given in combination with
pembrolizumab, 9% of the 121 patients treated with combination
therapy had pneumonitis/ILD of any grade and 3.3% had Grade 3. A
fatal event of pneumonitis occurred in one patient (0.8%). The
median time to onset of pneumonitis/ILD was 6 months (range: 0.6 to
26 months). Monitor patients for signs and symptoms indicative of
pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial
infiltrates on radiologic exams. Evaluate and exclude infectious,
neoplastic and other causes for such signs and symptoms through
appropriate investigations. Withhold PADCEV for patients who
develop Grade 2 pneumonitis/ILD and consider dose reduction.
Permanently discontinue PADCEV in all patients with Grade 3 or 4
pneumonitis/ILD.
Peripheral neuropathy (PN) Peripheral neuropathy occurred
in 53% of the 753 patients treated with PADCEV as a single agent in
clinical trials including 40% with sensory neuropathy, 7% with
muscular weakness and 7% with motor neuropathy. Thirty percent of
patients experienced Grade 2 reactions and 5% experienced Grade 3-4
reactions. Peripheral neuropathy occurred in patients treated with
PADCEV with or without preexisting peripheral neuropathy. The
median time to onset of Grade ≥2 peripheral neuropathy was 4.9
months (range: 0.1 to 20 months). Neuropathy led to treatment
discontinuation in 7% of patients. Of the patients who experienced
neuropathy who had data regarding resolution (N = 319), 14% had
complete resolution, 46% had partial improvement, and 40% had no
improvement at the time of their last evaluation. Of the 86% of
patients with residual neuropathy at last evaluation, 51% had Grade
2 or greater neuropathy at the time of their last evaluation. The
incidence of peripheral neuropathy occurred at a higher rate when
PADCEV was given in combination with pembrolizumab. When PADCEV was
given in combination with pembrolizumab, 65% of the 121 patients
treated with combination therapy had peripheral neuropathy of any
grade, 45% had Grade 2 neuropathy, and 3.3% had Grade 3 neuropathy.
The median time to onset of Grade ≥2 peripheral neuropathy was 6
months (range: 0.3 to 25 months). Monitor patients for symptoms of
new or worsening peripheral neuropathy and consider dose
interruption or dose reduction of PADCEV when peripheral neuropathy
occurs. Permanently discontinue PADCEV in patients who develop
Grade ≥3 peripheral neuropathy.
Ocular disorders were reported in 40% of the 384
patients treated with PADCEV as a single agent in clinical trials
in which ophthalmologic exams were scheduled. The majority of these
events involved the cornea and included events associated with dry
eye such as keratitis, blurred vision, increased lacrimation,
conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry
eye symptoms occurred in 34% of patients, and blurred vision
occurred in 13% of patients, during treatment with PADCEV. The
median time to onset to symptomatic ocular disorder was 1.6 months
(range: 0 to 19 months). Monitor patients for ocular disorders.
Consider artificial tears for prophylaxis of dry eyes and
ophthalmologic evaluation if ocular symptoms occur or do not
resolve. Consider treatment with ophthalmic topical steroids, if
indicated after an ophthalmic exam. Consider dose interruption or
dose reduction of PADCEV for symptomatic ocular disorders.
Infusion site extravasation Skin and soft tissue
reactions secondary to extravasation have been observed after
administration of PADCEV. Of the 753 patients treated with PADCEV
as a single agent in clinical trials, 1.5% of patients experienced
skin and soft tissue reactions, including 0.3% who experienced
Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling,
increased temperature, and pain worsened until 2-7 days after
extravasation and resolved within 1-4 weeks of peak. Two patients
(0.3%) developed extravasation reactions with secondary cellulitis,
bullae, or exfoliation. Ensure adequate venous access prior to
starting PADCEV and monitor for possible extravasation during
administration. If extravasation occurs, stop the infusion and
monitor for adverse reactions.
Embryo-fetal toxicity PADCEV can cause fetal harm
when administered to a pregnant woman. Advise patients of the
potential risk to the fetus. Advise female patients of reproductive
potential to use effective contraception during PADCEV treatment
and for 2 months after the last dose. Advise male patients with
female partners of reproductive potential to use effective
contraception during treatment with PADCEV and for 4 months after
the last dose.
Adverse Reactions
Most common adverse reactions, including laboratory
abnormalities (≥20%) (PADCEV monotherapy)
Rash, aspartate
aminotransferase increased, glucose increased, creatinine
increased, fatigue, peripheral neuropathy, lymphocytes decreased,
alopecia, decreased appetite, hemoglobin decreased, diarrhea,
sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia,
alanine aminotransferase increased, anemia, albumin decreased,
neutrophils decreased, urate increased, lipase increased, platelets
decreased, weight decreased and dry skin.
EV-301 Study: 296 patients previously treated with a PD-1/L1
inhibitor and platinum-based chemotherapy.
Serious adverse reactions occurred in 47% of patients treated with
PADCEV; the most common (≥2%) were urinary tract infection, acute
kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions
occurred in 3% of patients, including multiorgan dysfunction
(1.0%), hepatic dysfunction, septic shock, hyperglycemia,
pneumonitis and pelvic abscess (0.3% each). Adverse reactions
leading to discontinuation occurred in 17% of patients; the most
common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading
to dose interruption occurred in 61% of patients; the most common
(≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions
leading to dose reduction occurred in 34% of patients; the most
common (≥2%) were PN (10%), rash (8%), decreased appetite and
fatigue (3% each). Clinically relevant adverse reactions (<15%)
include vomiting li(14%), AST increased (12%), hyperglycemia (10%),
ALT increased (9%), pneumonitis (3%) and infusion site
extravasation (0.7%).
EV-201, Cohort 2 Study: 89 patients previously treated with a
PD-1/L1 inhibitor and not eligible for cisplatin-based
chemotherapy.
Serious adverse reactions occurred in 39% of
patients treated with PADCEV; the most common (≥3%) were pneumonia,
sepsis and diarrhea (5% each). Fatal adverse reactions occurred in
8% of patients, including acute kidney injury (2.2%), metabolic
acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis
(1.1% each). Adverse reactions leading to discontinuation occurred
in 20% of patients; the most common (≥2%) was PN (7%). Adverse
reactions leading to dose interruption occurred in 60% of patients;
the most common (≥3%) were PN (19%), rash (9%), fatigue (8%),
diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse
reactions leading to dose reduction occurred in 49% of patients;
the most common (≥3%) were PN (19%), rash (11%) and fatigue
(7%). Clinically relevant adverse reactions (<15%) include
vomiting (13%), AST increased (12%), lipase increased (11%), ALT
increased (10%), pneumonitis (4%) and infusion site extravasation
(1%).
EV-103 Study: 121 patients with previously untreated locally
advanced or metastatic urothelial cancer who were not eligible for
cisplatin-containing chemotherapy (PADCEV in combination with
pembrolizumab)
The most common adverse reactions,
including laboratory abnormalities (≥20%), of PADCEV in combination
with pembrolizumab were glucose increased, aspartate
aminotransferase increased, rash, hemoglobin decreased, creatinine
increased, peripheral neuropathy, lymphocytes decreased, fatigue,
alanine aminotransferase increased, sodium decreased, lipase
increased, albumin decreased, alopecia, phosphate decreased,
decreased weight, diarrhea, pruritus, decreased appetite, nausea,
dysgeusia, potassium decreased, neutrophils decreased, urinary
tract infection, constipation, potassium increased, calcium
increased, peripheral edema, dry eye, dizziness, arthralgia, and
dry skin.
Serious adverse reactions occurred in 50% of patients treated with
PADCEV in combination with pembrolizumab. The most common
serious adverse reactions (≥2%) were acute kidney injury (7%),
urinary tract infection (7%), urosepsis (5%), sepsis (3.3%),
pneumonia (3.3%), hematuria (3.3%), pneumonitis (3.3%), urinary
retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%),
myositis (2.5%), anemia (2.5%), and hypotension (2.5%). Fatal
adverse reactions occurred in 5% of patients treated with
PADCEV in combination with pembrolizumab including sepsis (1.6%),
bullous dermatitis (0.8%), myasthenia gravis (0.8%), and
pneumonitis/ILD (0.8%). Adverse reactions leading to
discontinuation of PADCEV occurred in 36% of patients. The most
common adverse reactions (≥2%) leading to discontinuation of
PADCEV were peripheral neuropathy (20%) and rash (6%). Adverse
reactions leading to dose interruption of PADCEV occurred in 69% of
patients. The most common adverse reactions (≥2%) leading to
dose interruption of PADCEV were peripheral neuropathy (18%),
rash (12%), lipase increased (6%), pneumonitis (6%), diarrhea
(4.1%), acute kidney injury (3.3%), alanine aminotransferase
increased (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract
infection (3.3%), amylase increased (2.5%), anemia (2.5%), COVID-19
(2.5%), hyperglycemia (2.5%), and hypotension (2.5%). Adverse
reactions leading to dose reduction of PADCEV occurred in 45% of
patients. The most common adverse reactions (≥2%) leading to
dose reduction of PADCEV were peripheral neuropathy (17%), rash
(12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%).
Drug Interactions
Effects of other drugs on
PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)
Concomitant use with dual P-gp and strong CYP3A4 inhibitors may
increase unconjugated monomethyl auristatin E exposure, which may
increase the incidence or severity of PADCEV toxicities. Closely
monitor patients for signs of toxicity when PADCEV is given
concomitantly with dual P-gp and strong CYP3A4 inhibitors.
Specific Populations
Lactation Advise lactating
women not to breastfeed during treatment with PADCEV and for at
least 3 weeks after the last dose.
Hepatic impairment Avoid the use of PADCEV in
patients with moderate or severe hepatic impairment.
For more information, please see the U.S. full Prescribing
Information including BOXED WARNING for
PADCEV here.
About Astellas
Astellas Pharma Inc. is a
pharmaceutical company conducting business in more than 70
countries around the world. We are promoting the Focus Area
Approach that is designed to identify opportunities for the
continuous creation of new drugs to address diseases with high
unmet medical needs by focusing on Biology and Modality.
Furthermore, we are also looking beyond our foundational Rx focus
to create Rx+® healthcare solutions that combine our
expertise and knowledge with cutting-edge technology in different
fields of external partners. Through these efforts, Astellas stands
on the forefront of healthcare change to turn innovative science
into VALUE for patients. For more information, please visit our
website at https://www.astellas.com/en.
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 seagen.com and follow us on
X and LinkedIn.
About the Seagen, Astellas and Merck
Collaboration
Seagen and Astellas entered a clinical
collaboration agreement with Merck to evaluate the combination of
Seagen's and Astellas' PADCEV® (enfortumab vedotin-ejfv)
and Merck's KEYTRUDA® (pembrolizumab) in patients with
previously untreated metastatic urothelial cancer. KEYTRUDA is a
registered trademark of Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc., Rahway,
NJ, USA.
Astellas Cautionary Notes
In this press release,
statements made with respect to current plans, estimates,
strategies and beliefs and other statements that are not historical
facts are forward-looking statements about the future performance
of Astellas. These statements are based on management's current
assumptions and beliefs in light of the information currently
available to it and involve known and unknown risks and
uncertainties. A number of factors could cause actual results to
differ materially from those discussed in the forward-looking
statements. Such factors include, but are not limited to: (i)
changes in general economic conditions and in laws and regulations,
relating to pharmaceutical markets, (ii) currency exchange rate
fluctuations, (iii) delays in new product launches, (iv) the
inability of Astellas to market existing and new products
effectively, (v) the inability of Astellas to continue to
effectively research and develop products accepted by customers in
highly competitive markets, and (vi) infringements of Astellas'
intellectual property rights by third parties.
Information about pharmaceutical products (including products
currently in development), which is included in this press release,
is not intended to constitute an advertisement or medical
advice.
Seagen Forward-Looking Statements
Certain statements
made in this press release are forward-looking, such as those,
among others, relating to the therapeutic potential of PADCEV,
alone or in combination; its possible efficacy, safety and
therapeutic uses; the potential for results from the EV-302 trial
to serve as the confirmatory trial to convert the U.S. accelerated
approval to standard approval, expand the indication into the
cisplatin-eligible patient population and serve as the basis for
global regulatory submissions; planned and ongoing clinical trials;
and the development program for PADCEV. 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 possibility that data
from the EV-302 trial may not be sufficient to convert U.S.
accelerated approval to standard approval, to expand the indication
into the cisplatin-ineligible population or to support global
regulatory approvals; adverse events and newly-emerging safety
signals; adverse regulatory actions; delays, setbacks or failures
in product development activities and the regulatory review process
for a variety of reasons, including, without limitation, the
inherent difficulty and uncertainty of pharmaceutical product
development; possible required modifications to clinical trials;
failure to properly conduct or manage clinical trials; and failure
of clinical results to support continued development or regulatory
approvals. More information about the risks and uncertainties faced
by Seagen is contained under the caption "Risk Factors" included in
the company's Quarterly Report on Form 10-Q for the quarter ended
September 30, 2023 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 law.
i Key statistics for Bladder Cancer. American
Cancer Society. (n.d.).
https://www.cancer.org/cancer/types/bladder-cancer/about/key-statistics.html
ii National Cancer Institute. What is bladder cancer?
https://www.cancer.gov/types/bladder#:~:text=Types%20of%20bladder%20cancer,bladder%20cancers%20are%20urothelial%20carcinomas.
Accessed October 30, 2023.
iiiNational Cancer Institute. Cancer stat facts: bladder
cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed
October 30, 2023.
iv Galsky MD, Pal SK, Lin SW, Ogale S, et al.
(2018). Real-world effectiveness of chemotherapy in elderly
patients with metastatic bladder cancer in the United States. Bladder Cancer
4(2):227-38.
v American Society of Clinical Oncology. Bladder
cancer: introduction (12-2021).
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
Accessed October 30, 2023.
vi International Agency for Research on
Cancer. Cancer Today: bladder globocan 2020 fact sheet
(12-2020).
https://gco.iarc.fr/today/data/factsheets/cancers/30-Bladder-fact-sheet.pdf.
Accessed October 30, 2023.
vii Challita-Eid PM, Satpayev D, Yang P, et al.
Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a
highly potent therapeutic agent in multiple preclinical cancer
models. Cancer Res 2016;76(10):3003-13.
viii PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
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