– PADCEV plus pembrolizumab approved based
on groundbreaking EV-302 trial –
– Confirmatory trial found PADCEV plus
pembrolizumab nearly doubled median overall survival compared to
standard of care platinum-based chemotherapy –
Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE:4503,
President and CEO: Naoki Okamura, "Astellas") today announced that
on December 15, 2023 the U.S. Food and Drug Administration (FDA)
has approved PADCEV® (enfortumab vedotin-ejfv, an antibody-drug
conjugate [ADC]) with KEYTRUDA® (pembrolizumab, a PD-1 inhibitor)
for the treatment of adult patients with locally advanced or
metastatic urothelial cancer (la/mUC). This combination is the
first approved to offer an alternative to platinum-containing
chemotherapy, the current standard of care in first-line
la/mUC.
The approval is based on results from the Phase 3 EV-302
clinical trial (also known as KEYNOTE-A39), which demonstrated the
combination nearly doubled median overall survival (OS) and median
progression-free survival (PFS) in patients with previously
untreated la/mUC compared to platinum-containing chemotherapy.
Findings from EV-302 were presented at the European Society for
Medical Oncology (ESMO) Congress 2023. EV-302 also serves as the
confirmatory trial for the U.S. accelerated approval of this
combination for adult patients with la/mUC who are not eligible to
receive cisplatin-containing chemotherapy (approved in April 2023)
and expands the labeled indication to include patients who are
eligible to receive cisplatin chemotherapy. EV-302 is also serving
as the basis for global submissions.
Roger Dansey, M.D., Chief Development Officer, Oncology,
Pfizer
“In the Phase 3 EV-302 study, the combination of PADCEV and
pembrolizumab demonstrated survival benefit for patients with
advanced bladder cancer, nearly doubling median OS and median PFS
compared with chemotherapy. We hope the approval of this
combination will transform the standard of care for advanced
bladder cancer and give patients more time with their loved
ones.”
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of
Oncology Development, Astellas
“Today’s FDA approval represents a paradigm change in the
treatment of advanced bladder cancer and provides hope to the
thousands of Americans impacted by this aggressive disease. This
achievement is notable, as it is the first regimen approved in
advanced urothelial cancer that has demonstrated superiority to
platinum chemotherapy, the gold standard of care for decades.”
The EV-302 study met its dual primary endpoints of OS and PFS
compared to platinum-containing chemotherapy. Treatment with the
combination resulted in a median OS of 31.5 months (95% CI:
25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) with
chemotherapy, representing a 53% reduction in risk of death (Hazard
Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58;
P<0.00001). The median PFS of 12.5 months (95% CI: 10.4-16.6)
with the combination compared to 6.3 months (95% CI: 6.2-6.5) with
chemotherapy represents a 55% reduction in the risk of cancer
progression or death (HR=0.45; 95% CI: (0.38-0.54); P<0.00001).
Consistent OS and PFS results were observed across pre-defined
subgroups, including cisplatin eligibility and PD-L1 expression
level. Cisplatin eligible and ineligible subgroups (n=244 and 198,
respectively) saw a 47% and 57% reduced risk of death,
respectively, and a 52% and 57% reduced risk of progression or
death, respectively. PD-L1 and high PD-L1 expression subgroups
(n=184 and 254, respectively) saw a 56% and 51% reduced risk of
death, respectively, and a 50% and 58% reduced risk of progression
or death, respectively.
The most common (≥20%) all-grade adverse events (AEs), including
laboratory abnormalities, related to treatment with enfortumab
vedotin and pembrolizumab were increased aspartate
aminotransferase, increased creatinine, rash, increased glucose,
peripheral neuropathy, increased lipase, decreased lymphocytes,
increased alanine aminotransferase, 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. The safety results in EV-302 are
consistent with those previously reported with this combination in
EV-103 in cisplatin-ineligible patients with la/mUC. 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).
Thomas Powles, M.R.C.P., M.D., Professor of Genitourinary
Oncology at Queen Mary University of London; Director, Barts Cancer
Center, London; EV-302 Primary Investigator
“Advanced bladder cancer is a common cause of cancer-related
death. The overall survival benefit seen in the EV-302 trial
demonstrates the potential for PADCEV in combination with
pembrolizumab to impact first-line treatment of patients with
locally advanced or metastatic urothelial carcinoma. In my opinion,
this is a meaningful advancement over platinum-based chemotherapy
in the systemic treatment of these patients.”
Andrea Maddox-Smith, CEO, Bladder Cancer Advocacy Network
(BCAN)
“Despite advances in the treatment of advanced bladder cancer,
there remains a need for therapies that extend patients’ lives. Our
network is thrilled that the FDA has approved a new treatment
option, and we are excited about the hope it will provide to
members of the bladder cancer patient community.”
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 objective response rate (ORR) and duration of response
(DOR) per RECIST v1.1 by BICR, and safety.
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.i
- 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. ii
- Globally, approximately 573,000 new cases of bladder cancer and
212,000 deaths are reported annually.iii
- It is estimated that approximately 82,290 people in the U.S.
will be diagnosed with bladder cancer in 2023.iv
- 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.v
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.vi 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).vii
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 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 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 the Pfizer, 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. 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.
Pfizer Disclosure Notice
The information contained in this release is as of December 15,
2023. 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, and an approval in the U.S. of
PADCEV with pembrolizumab for the treatment of adult patients with
locally advanced or metastatic urothelial cancer (la/mUC) and
ongoing investigational trials for PADCEV 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
with pembrolizumab; 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; whether and when any applications that may be
pending or filed for PADCEV with pembrolizumab 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 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; 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.
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.
________________________
i National Cancer Institute. What is
bladder cancer?
https://www.cancer.gov/types/bladder#:~:text=Types%20of%20bladder%20cancer,bladder%20cancers%20are%20urothelial%20carcinomas.
ii American Society of Clinical Oncology.
Bladder cancer: introduction (12-2021).
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
iii 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.
iv Siegel RL, Miller KD, Wagle NS, Jemal
A. Cancer statistics, 2023. CA Cancer J Clin 2023;73(1):17-48.
v National Cancer Institute. Cancer stat
facts: bladder cancer.
https://seer.cancer.gov/statfacts/html/urinb.html
vi 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.
vii PADCEV [package insert]. Northbrook,
IL: Astellas Pharma US, Inc.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231215417518/en/
Pfizer Contacts: For Media 212-733-1226
PfizerMediaRelations@Pfizer.com
For Investors 212-733-4848 IR@pfizer.com
Astellas Contacts: For Media Elysia Wood (703) 722-4656
elysia.wood@astellas.com
For Investors Astellas Pharma Inc. Corporate Communications
+81-3-3244-3202
Pfizer (NYSE:PFE)
Gráfico Histórico do Ativo
De Abr 2024 até Mai 2024
Pfizer (NYSE:PFE)
Gráfico Histórico do Ativo
De Mai 2023 até Mai 2024