- First-in-Class Antibody-Drug
Conjugate Directed Against Nectin-4, a Protein Highly Expressed in
Urothelial Tumors1,2 -
- PADCEV is the First Treatment Approved for
Locally Advanced or Metastatic Urothelial Cancer Following
Treatment with Platinum-based Chemotherapy and a PD-1 or PD-L1
Inhibitor -
Seattle Genetics, Inc. (Nasdaq:SGEN) and Astellas Pharma Inc.
(TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”)
today announced that the U.S. Food and Drug Administration (FDA)
granted accelerated approval to PADCEV™ for the treatment of adult
patients with locally advanced or metastatic urothelial cancer who
have previously received a PD-1/L1 inhibitor and a
platinum-containing chemotherapy before (neoadjuvant) or after
(adjuvant) surgery or in a locally advanced or metastatic setting.
PADCEV is approved under the FDA’s Accelerated Approval Program
based on tumor response rate. Continued approval may be contingent
upon verification and description of clinical benefit in
confirmatory trials. PADCEV is the first FDA approved treatment in
the U.S. for these patients. It 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.1,3
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20191218005817/en/
(Photo: Business Wire)
“Metastatic urothelial cancer is an aggressive and devastating
disease with limited treatment options, and the approval of PADCEV
is a significant advance for these patients who previously had
limited options after initial therapies failed,” said Jonathan E.
Rosenberg, M.D., Medical Oncologist, Chief, Genitourinary Medical
Oncology Service, Memorial Sloan Kettering Cancer Center in New
York. “The PADCEV clinical trial enrolled a range of patients whose
cancer was difficult to treat, including those whose disease had
spread to the liver.”
“The FDA approval of PADCEV is welcome news for patients with
bladder cancer,” said Andrea Maddox-Smith, Chief Executive Officer,
Bladder Cancer Advocacy Network. “Though new medicines for bladder
cancer have been approved in recent years, most people living with
advanced stages of this disease face a difficult journey with few
treatment options.”
“This approval underscores our commitment to develop novel
medicines that address unmet patient needs, and we’re grateful to
the patients and physicians whose participation led to this
outcome,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President
and Oncology Therapeutic Area Head, Astellas.
“PADCEV is the first antibody-drug conjugate approved for
patients facing this aggressive disease, and it is the culmination
of years of innovative work on this technology,” said Roger Dansey,
M.D., Chief Medical Officer, Seattle Genetics.
PADCEV was evaluated in the pivotal trial EV-201, a single-arm
phase 2 multi-center trial that enrolled 125 patients with locally
advanced or metastatic urothelial cancer who received prior
treatment with a PD-1 or PD-L1 inhibitor and a platinum-based
chemotherapy.1 In the study, the primary endpoint of confirmed
objective response rate (ORR) was 44 percent per blinded
independent central review (55/125; 95% Confidence Interval [CI]:
35.1, 53.2). Among patients treated with the single agent PADCEV,
12 percent (15/125) experienced a complete response, meaning no
cancer could be detected at the time of assessment, and 32 percent
(40/125) experienced a partial response, meaning a decrease in
tumor size or extent of cancer in the body. The median duration of
response (DoR), a secondary endpoint, was 7.6 months (95% CI: 6.3,
not estimable [NE]). The most common serious adverse reactions
(≥3%) were urinary tract infection (6%), cellulitis (5%), febrile
neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury
(3%), dyspnea (3%), and rash (3%). The most common adverse reaction
leading to discontinuation was peripheral neuropathy (6%). The most
common adverse reactions (≥20%) were fatigue (56%), peripheral
neuropathy (56%), decreased appetite (52%), rash (52%), alopecia
(50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye
(40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3
adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue
(6%).
The FDA's Accelerated Approval Program allows approval of a
medicine based on a surrogate endpoint if the medicine fills an
unmet medical need for a serious condition. A global, randomized
phase 3 confirmatory clinical trial (EV-301) is underway and is
also intended to support global registrations.
About PADCEV
PADCEV 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.1,2 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). PADCEV is
co-developed by Astellas and Seattle Genetics.
PADCEV Support Solutions offers access and reimbursement support
to help patients access PADCEV. For more information, go to PADCEV
Support Solutions at PADCEVSupportSolutions.com.
About Bladder and Urothelial Cancer
Approximately 80,000 people in the U.S. will be diagnosed with
bladder cancer this year.4 Urothelial cancer accounts for 90
percent of all bladder cancers and can also be found in the renal
pelvis, ureter and urethra.5
Important Safety Information
Warnings and Precautions
- Hyperglycemia occurred in patients treated with PADCEV,
including death and diabetic ketoacidosis (DKA), in those with and
without pre-existing diabetes mellitus. The incidence of Grade 3-4
hyperglycemia increased consistently in patients with higher body
mass index and in patients with higher baseline A1C. In one
clinical trial, 8% of patients developed Grade 3-4 hyperglycemia.
Patients with baseline hemoglobin A1C ≥8% were excluded. 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.
- Peripheral neuropathy (PN), predominantly sensory,
occurred in 49% of the 310 patients treated with PADCEV in clinical
trials; 2% experienced Grade 3 reactions. In one clinical trial,
peripheral neuropathy occurred in patients treated with PADCEV with
or without preexisting peripheral neuropathy. The median time to
onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy
led to treatment discontinuation in 6% of patients. At the time of
their last evaluation, 19% had complete resolution, and 26% had
partial improvement. 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 that develop Grade ≥3
peripheral neuropathy.
- Ocular disorders occurred in 46% of the 310 patients
treated with PADCEV. The majority of these events involved the
cornea and included keratitis, blurred vision, limbal stem cell
deficiency and other events associated with dry eyes. Dry eye
symptoms occurred in 36% of patients, and blurred vision occurred
in 14% of patients, during treatment with PADCEV. The median time
to onset to symptomatic ocular disorder was 1.9 months (range: 0.3
to 6.2). 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.
- Skin reactions occurred in 54% of the 310 patients
treated with PADCEV in clinical trials. Twenty-six percent (26%) of
patients had maculopapular rash and 30% had pruritus. Grade 3-4
skin reactions occurred in 10% of patients and included symmetrical
drug-related intertriginous and flexural exanthema (SDRIFE),
bullous dermatitis, exfoliative dermatitis, and palmar-plantar
erythrodysesthesia. In one clinical trial, the median time to onset
of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the
patients who experienced rash, 65% had complete resolution and 22%
had partial improvement. Monitor patients for skin reactions.
Consider appropriate treatment, such as topical corticosteroids and
antihistamines for skin reactions, as clinically indicated. For
severe (Grade 3) skin reactions, withhold PADCEV until improvement
or resolution and administer appropriate medical treatment.
Permanently discontinue PADCEV in patients that develop Grade 4 or
recurrent Grade 3 skin reactions.
- Infusion site extravasation Skin and soft tissue
reactions secondary to extravasation have been observed after
administration of PADCEV. Of the 310 patients, 1.3% of patients
experienced skin and soft tissue 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. One percent (1%) of patients 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
Serious adverse reactions occurred in 46% of patients treated
with PADCEV. The most common serious adverse reactions (≥3%) were
urinary tract infection (6%), cellulitis (5%), febrile neutropenia
(4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea
(3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of
patients, including acute respiratory failure, aspiration
pneumonia, cardiac disorder, and sepsis (each 0.8%).
Adverse reactions leading to discontinuation occurred in 16% of
patients; the most common adverse reaction leading to
discontinuation was peripheral neuropathy (6%). Adverse reactions
leading to dose interruption occurred in 64% of patients; the most
common adverse reactions leading to dose interruption were
peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse
reactions leading to dose reduction occurred in 34% of patients;
the most common adverse reactions leading to dose reduction were
peripheral neuropathy (12%), rash (6%) and fatigue (4%).
The most common adverse reactions (≥20%) were fatigue (56%),
peripheral neuropathy (56%), decreased appetite (52%), rash (52%),
alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry
eye (40%), pruritus (26%) and dry skin (26%). The most common Grade
≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and
fatigue (6%).
Lab Abnormalities
In one clinical trial, Grade 3-4 laboratory abnormalities
reported in ≥5% were: lymphocytes decreased, hemoglobin decreased,
phosphate decreased, lipase increased, sodium decreased, glucose
increased, urate increased, neutrophils decreased.
Drug Interactions
- Effects of other drugs on PADCEV Concomitant use
with a strong CYP3A4 inhibitor may increase free MMAE exposure,
which may increase the incidence or severity of PADCEV toxicities.
Closely monitor patients for signs of toxicity when PADCEV is given
concomitantly with 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 full Prescribing
Information for PADCEV here.
About Seattle Genetics
Seattle Genetics, Inc. is an emerging multi-product, global
biotechnology company that develops and commercializes
transformative therapies targeting cancer to make a meaningful
difference in people’s lives. The company is headquartered in
Bothell, Washington, and has a European office in Switzerland. For
more information on our robust pipeline, visit
www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
About Astellas
Astellas Pharma Inc., based in Tokyo, Japan, is a company
dedicated to improving the health of people around the world
through the provision of innovative and reliable pharmaceutical
products. For more information, please visit our website at
https://www.astellas.com/en.
About the Seattle Genetics and Astellas Collaboration
Seattle Genetics and Astellas are co-developing PADCEV
(enfortumab vedotin) under a collaboration that was entered into in
2007 and expanded in 2009. Under the collaboration, the companies
are sharing costs and profits on a 50:50 basis worldwide.
Seattle Genetics Forward Looking Statements
Certain statements made in this press release are forward
looking, such as those, among others, relating to the continued FDA
approval of PADCEV™ (enfortumab vedotin-ejfv) for the treatment of
adult patients with locally advanced or metastatic urothelial
cancer who have previously received a PD-1/L1 inhibitor, and a
platinum-containing chemotherapy in the neoadjuvant/adjuvant,
locally advanced or metastatic setting; the conduct of an ongoing
randomized phase 3 confirmatory clinical trial (EV-301) intended to
verify the clinical benefit of PADCEV and support global
registrations; and the therapeutic potential of PADCEV including
its efficacy, safety and therapeutic uses. Actual results or
developments may differ materially from those projected or implied
in these forward-looking statements. Factors that may cause such a
difference include the possibility that EV-301 and subsequent
clinical trials may fail to establish sufficient efficacy; that
adverse events or safety signals may occur; that utilization and
adoption of PADCEV by prescribing physicians may be limited by the
availability and extent of reimbursement or other factors; and that
adverse regulatory actions may occur. More information about the
risks and uncertainties faced by Seattle Genetics is contained
under the caption “Risk Factors” included in the company’s
Quarterly Report on Form 10-Q for the quarter ended September 30,
2019 filed with the Securities and Exchange Commission. Seattle
Genetics disclaims any intention or obligation to update or revise
any forward-looking statements, whether as a result of new
information, future events or otherwise, except as required by
law.
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.
1 PADCEV [package insert]. Northbrook, IL: Astellas, Inc. 2
Rosenberg JE, O’Donnell PH, Balar AV, et al. Pivotal Trial of
Enfortumab Vedotin in Urothelial Carcinoma After Platinum and
Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin
Oncol 2019;37(29):2592-600. 3 Challita-Eid P, 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. 4
American Society of Clinical Oncology. Bladder cancer: introduction
(10-2017).
https://www.cancer.net/cancer-types/bladdercancer/introduction.
Accessed 05-09-2019. 5 National Cancer Institute. Surveillance,
Epidemiology, and End Results Program. Cancer stat facts: bladder
cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed
05-01-2019.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191218005817/en/
Seattle Genetics Contacts: For Media Monique Greer Vice
President, Corporate Communications (425) 527-4641
mgreer@seagen.com
For Investors Peggy Pinkston Vice President, Investor Relations
(425) 527-4160 ppinkston@seagen.com
Astellas Contacts: For Media Marjorie Moeling Director,
Corporate Affairs (224) 205-5205 marjorie.moeling@astellas.com
For Investors Shin Okubo Executive Director, Investor Relations
+81-3-3244-3202 shin.ohkubo@astellas.com
Seagen (NASDAQ:SGEN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Seagen (NASDAQ:SGEN)
Historical Stock Chart
From Apr 2023 to Apr 2024