– Pivotal trial found the
enfortumab vedotin plus pembrolizumab combination
significantly extended overall and progression-free survival
–
– If approved, PADCEV with KEYTRUDA would
be the first combination in the EU to offer an alternative to
platinum-containing chemotherapy, the current standard of care in
first-line locally advanced or metastatic urothelial cancer
–
TOKYO and NEW
YORK, Jan. 26, 2024 /PRNewswire/ -- Astellas
Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura,
"Astellas") and Pfizer Inc. (NYSE: PFE) today announced that on
Jan. 26, 2024 the European
Medicines Agency (EMA) validated for review a Type II variation
application for PADCEV™ (enfortumab vedotin) with
KEYTRUDA® (pembrolizumab) as a combination therapy for
the first-line treatment of adult patients with previously
untreated locally advanced or metastatic urothelial cancer
(la/mUC). If approved, PADCEV with KEYTRUDA has the potential to
change the treatment paradigm, becoming the first combination
treatment to offer an alternative to platinum-containing
chemotherapy, the current standard of care in first-line
la/mUC.
Globally, approximately 573,000 new cases of bladder cancer and
212,000 deaths are reported annually.1
It
is estimated that approximately 200,000 people in Europe are diagnosed with bladder cancer each
year.2
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of
Oncology Development, Astellas
"Patients in Europe need better treatment options for
advanced stage urothelial cancer, and we look forward to working
with the EMA on their review of the combination of enfortumab
vedotin and pembrolizumab. If approved, the combination would be
the first alternative to a chemotherapy-based treatment for this
patient population. This milestone is another opportunity to affirm
our commitment to helping patients with advanced urothelial cancer
live longer."
Roger Dansey, M.D., Chief
Development Officer, Oncology, Pfizer
"The EV-302 pivotal
trial demonstrated the benefits of combining PADCEV with
pembrolizumab for advanced bladder cancer. Patients with bladder
cancer in Europe face poor
outcomes at the advanced stage, and innovative therapies that
extend survival are needed. This acceptance brings us closer to our
mission: delivering breakthroughs that help address the unmet needs
of patients and reshape the advanced urothelial cancer treatment
landscape."
The Type II variation application 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 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.
The EMA's Committee for Medicinal Products for Human Use (CHMP)
and subsequently the European Commission (EC) are expected to
share their opinions and decisions on the Type II variation
application in calendar year 2024. The U.S. Food and Drug
Administration approved the combination therapy in December 2023.
About EV-302
The EV-302 trial is an open-label,
randomized, controlled Phase 3 study, evaluating enfortumab vedotin
in combination with pembrolizumab versus platinum-containing
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
platinum- containing 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 ORR per
RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.
The EV-302 trial is part of an extensive clinical 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.3
- 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.4
- Urothelial cancer accounts for 90% of all bladder cancers and
can also be found in the renal pelvis, ureter, and
urethra.3
- Approximately 12% of cases are locally advanced or metastatic
urothelial cancer at diagnosis.5
Ongoing Investigational Trials
The EV-302 trial
(NCT04223856) is an open-label, randomized, controlled Phase 3
study, evaluating 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 second-line urothelial
cancer and 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)
PADCEV
(enfortumab vedotin) is a first-in-class antibody-drug conjugate
(ADC) that is directed against Nectin-4, a protein located on the
surface of cells and highly expressed in bladder
cancer.6 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).7
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®, in combination with pembrolizumab, is
indicated for the treatment of adult patients with locally advanced
or metastatic urothelial cancer (mUC).
PADCEV, as a single agent, is indicated for the treatment of
adult patients with locally advanced or 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.
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
70% (all grades) of the 564 patients treated with PADCEV in
combination with pembrolizumab in clinical trials. When PADCEV was
given in combination with pembrolizumab, the incidence of skin
reactions, including severe events, occurred at a higher rate
compared to PADCEV as a single agent. 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 17% of patients (Grade 3: 16%, Grade 4: 1%),
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 (0.2%). The median time to onset
of severe skin reactions was 1.7 months (range: 0.1 to 17.2
months). Skin reactions led to discontinuation of PADCEV in 6% of
patients.
Skin reactions occurred in 58% (all grades) of the 720 patients
treated with PADCEV as a single agent in clinical trials.
Twenty-three percent (23%) of patients had maculo-papular rash and
34% had pruritus. Grade 3-4 skin reactions occurred in 14% 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 0.6 months (range: 0.1 to 8 months).
Among patients experiencing a skin reaction leading to dose
interruption who then restarted PADCEV (n=75), 24% of patients
restarting at the same dose and 24% of patients restarting at a
reduced dose experienced recurrent severe skin reactions. Skin
reactions led to discontinuation of PADCEV in 3.1% 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), 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,
17% of the 720 patients treated with PADCEV developed hyperglycemia
of any grade; 7% of patients developed Grade 3-4 hyperglycemia
(Grade 3: 6.5%, Grade 4: 0.6%). Fatal events of hyperglycemia and
DKA 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. The median
time to onset of hyperglycemia was 0.5 months (range: 0 to 20
months). Hyperglycemia led to discontinuation of PADCEV in 0.7% of
patients. Five percent (5%) of patients required initiation of
insulin therapy for treatment of hyperglycemia. Of the patients who
initiated insulin therapy for treatment of hyperglycemia, 66%
(23/35) discontinued insulin at the time of last evaluation.
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. When PADCEV was given in combination with
pembrolizumab, 10% of the 564 patients treated with combination
therapy had pneumonitis/ILD of any grade and 4% had Grade 3-4. A
fatal event of pneumonitis/ILD occurred in two patients (0.4%). The
incidence of pneumonitis/ILD, including severe events, occurred at
a higher rate when PADCEV was given in combination with
pembrolizumab compared to PADCEV as a single agent. The median time
to onset of any grade pneumonitis/ILD was 4 months (range: 0.3 to
26 months).
In clinical trials of PADCEV as a single agent, 3% of the 720
patients treated with PADCEV had pneumonitis/ILD of any grade and
0.8% had Grade 3-4. The median time to onset of any grade
pneumonitis/ILD was 2.9 months (range: 0.6 to 6 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) When PADCEV was given in
combination with pembrolizumab, 67% of the 564 patients treated
with combination therapy had PN of any grade, 36% had Grade 2
neuropathy, and 7% had Grade 3 neuropathy. The incidence of PN
occurred at a higher rate when PADCEV was given in combination with
pembrolizumab compared to PADCEV as a single agent. The median time
to onset of Grade ≥2 PN was 6 months (range: 0.3 to 25 months).
PN occurred in 53% of the 720 patients treated with PADCEV as a
single agent in clinical trials including 38% with sensory
neuropathy, 8% with muscular weakness and 7% with motor neuropathy.
Thirty percent of patients experienced Grade 2 reactions and 5%
experienced Grade 3-4 reactions. PN occurred in patients treated
with PADCEV with or without preexisting PN. The median time to
onset of Grade ≥2 PN was 4.9 months (range: 0.1 to 20 months).
Neuropathy led to treatment discontinuation in 6% of patients.
Monitor patients for symptoms of new or worsening PN and
consider dose interruption or dose reduction of PADCEV when PN
occurs. Permanently discontinue PADCEV in patients who develop
Grade ≥3 PN.
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 30% of patients, and blurred vision
occurred in 10% of patients, during treatment with PADCEV. The
median time to onset to symptomatic ocular disorder was 1.7 months
(range: 0 to 30.6 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 720 patients treated with PADCEV
as a single agent in clinical trials, 1% 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 in combination with
pembrolizumab) Increased aspartate aminotransferase (AST),
increased creatinine, rash, increased glucose, PN, increased
lipase, decreased lymphocytes, increased alanine aminotransferase
(ALT), decreased hemoglobin, fatigue, decreased sodium, decreased
phosphate, decreased albumin, pruritus, diarrhea, alopecia,
decreased weight, decreased appetite, increased urate, decreased
neutrophils, decreased potassium, dry eye, nausea, constipation,
increased potassium, dysgeusia, urinary tract infection and
decreased platelets.
Most common adverse reactions, including laboratory
abnormalities (≥20%) (PADCEV monotherapy) Increased
glucose, increased AST, decreased lymphocytes, increased
creatinine, rash, fatigue, PN, decreased albumin, decreased
hemoglobin, alopecia, decreased appetite, decreased neutrophils,
decreased sodium, increased ALT, decreased phosphate, diarrhea,
nausea, pruritus, increased urate, dry eye, dysgeusia,
constipation, increased lipase, decreased weight, decreased
platelets, abdominal pain, dry skin.
EV-302 Study: 440 patients with previously untreated la/mUC
(PADCEV in combination with pembrolizumab)
Serious adverse reactions occurred in 50% of
patients treated with PADCEV in combination with pembrolizumab. The
most common serious adverse reactions (≥2%) were rash (6%), acute
kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection
(3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and
hyperglycemia (2%). Fatal adverse
reactions occurred in 3.9% of patients treated with PADCEV
in combination with pembrolizumab including acute respiratory
failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).
Adverse reactions leading to discontinuation of PADCEV occurred
in 35% of patients. The most common adverse reactions (≥2%)
leading to discontinuation of PADCEV were PN (15%), rash
(4.1%) and pneumonitis/ILD (2.3%). Adverse reactions leading to
dose interruption of PADCEV occurred in 73% of patients.
The most common adverse reactions (≥2%) leading to dose
interruption of PADCEV were PN (22%), rash (16%), COVID-19
(10%), diarrhea (5%), pneumonitis/ILD (4.8%), fatigue (3.9%),
hyperglycemia (3.6%), increased ALT (3%) and pruritus (2.5%).
Adverse reactions leading to dose reduction of PADCEV occurred in
42% of patients. The most common adverse reactions (≥2%)
leading to dose reduction of PADCEV were rash (16%), PN
(13%) and fatigue (2.7%).
EV-103 Study: 121 patients with previously untreated la/mUC
who were not eligible for cisplatin-containing chemotherapy (PADCEV
in combination with pembrolizumab)
Serious adverse reactions occurred in 50% of
patients treated with PADCEV in combination with pembrolizumab; the
most common (≥2%) were acute kidney injury (7%), urinary tract
infection (7%), urosepsis (5%), sepsis (3.3%), pneumonia (3.3%),
hematuria (3.3%), pneumonitis/ILD (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 (≥2%) were PN (20%) and rash (6%). Adverse
reactions leading to dose interruption of PADCEV occurred
in 69% of patients; the most common (≥2%) were PN (18%), rash
(12%), increased lipase (6%), pneumonitis/ILD (6%), diarrhea
(4.1%), acute kidney injury (3.3%), increased ALT (3.3%), fatigue
(3.3%), neutropenia (3.3%), urinary tract infection (3.3%),
increased amylase (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 (≥2%) were PN (17%), rash (12%),
fatigue (5%), neutropenia (5%), and diarrhea (4.1%).
EV-301 Study: 296 patients previously treated with a PD-1/L1
inhibitor and platinum-based chemotherapy (PADCEV
monotherapy)
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%), hepatic
dysfunction, septic shock, hyperglycemia, pneumonitis/ILD, 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).
EV-201, Cohort 2 Study: 89 patients previously treated with a
PD-1/L1 inhibitor and not eligible for cisplatin-based chemotherapy
(PADCEV monotherapy)
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/ILD (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%),
increased AST, 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%).
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 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 Pfizer Oncology
At Pfizer Oncology, we are at
the forefront of a new era in cancer care. Our industry-leading
portfolio and extensive pipeline includes game-changing mechanisms
of action to attack cancer from multiple angles, including
antibody-drug conjugates (ADCs), small molecules, bispecifics and
other immunotherapies. We are focused on delivering transformative
therapies in some of the world's most common cancers, including
breast cancer, genitourinary cancer and hematologic malignancies,
as well as melanoma, gastrointestinal, gynecological and thoracic
cancers, which includes lung cancer. Driven by science, we are
committed to accelerating breakthroughs to extend and improve
patients' lives.
About the Astellas, Pfizer and Merck
Collaboration
Astellas and Seagen entered a clinical
collaboration agreement with Merck to evaluate the combination of
Astellas' and Seagen's PADCEVTM (enfortumab
vedotin) and Merck's KEYTRUDA® (pembrolizumab) in
patients with previously untreated metastatic urothelial cancer. As
previously announced, Pfizer Inc. successfully completed its
acquisition of Seagen on December 14,
2023. KEYTRUDA is a registered trademark of Merck Sharp
& Dohme Corp., a subsidiary of Merck & Co., Inc.,
Rahway, NJ, USA (known as MSD
outside of the United States and
Canada).
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.
Pfizer Disclosure Notice
The information contained
in this release is as of January 26,
2024. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new
information or future events or developments.
This release contains forward-looking information about
Pfizer Oncology, PADCEV (enfortumab vedotin-ejfv, an antibody-drug
conjugate [ADC]) and KEYTRUDA® (pembrolizumab, a
PD-1 inhibitor), including its potential benefits, a Type II
variation application pending with European Medicines Agency for
Padcev and pembrolizumab as a combination therapy for the
first-line treatment of adult patients with previously untreated
locally advanced or metastatic urothelial cancer and ongoing
investigational trials for PADCEV alone or in combination with
pembrolizumab, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of PADCEV; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical
trials, regulatory submission dates, regulatory approval dates
and/or launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the
risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when drug
applications may be filed in particular jurisdictions for PADCEV
with pembrolizumab or as a single agent; whether and when any
applications that may be pending or filed for PADCEV with
pembrolizumab, including the Type II variation application, or as a
single agent, may be approved by regulatory authorities, which will
depend on myriad factors, including making a determination as to
whether the product's benefits outweigh its known risks and
determination of the product's efficacy and, if approved, whether
PADCEV with pembrolizumab or as a single agent will be commercially
successful; decisions by regulatory authorities impacting labeling,
manufacturing processes, safety and/or other matters that could
affect the availability or commercial potential of PADCEV with
pembrolizumab or as a single agent; whether the collaboration
between Pfizer, Astellas and Merck will be successful;
uncertainties regarding the impact of COVID-19 on Pfizer's
business, operations and financial results; and competitive
developments.
A further description of risks and uncertainties can be found
in Pfizer's Annual Report on Form 10-K for the fiscal year ended
December 31, 2022 and in its
subsequent reports on Form 10-Q, including in the sections thereof
captioned "Risk Factors" and "Forward-Looking Information and
Factors That May Affect Future Results", as well as in its
subsequent reports on Form 8-K, all of which are filed with the
U.S. Securities and Exchange Commission and available at
www.sec.gov and www.pfizer.com.
1 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.
2 Bladder cancer: The forgotten cancer. Uroweb. (n.d.).
https://uroweb.org/news/bladder-cancer-the-forgotten-cancer.
3 National Cancer Institute. What is bladder cancer?
https://www.cancer.gov/types/bladder#:~:text=Types%20of%20bladder%20cancer,bladder%20cancers%20are%20urothelial%20carcinomas.
4 American Society of Clinical Oncology. Bladder cancer:
introduction
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