TOKYO and BOTHELL, Wash., June 3,
2019 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503)
(President and CEO: Kenji Yasukawa,
Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:
SGEN) today announced that data from the first cohort of
a pivotal phase 2 clinical trial known as EV-201 demonstrated
that the investigational agent enfortumab vedotin rapidly shrank
tumors in most patients, resulting in an objective response rate
(ORR) of 44 percent (55/125; 95% Confidence Interval (CI):
35.1-53.2). Complete responses (CR) were observed in 12 percent of
patients (15/125). The median duration of tumor response was 7.6
months (range 0.95-11.3+). This cohort was open to patients with
locally advanced or metastatic urothelial cancer who had received
previous treatment with a platinum-containing chemotherapy and a
PD-1/L1 checkpoint inhibitor. Responses were similar in the
subgroups of patients analyzed, including those who had the worst
prognosis, such as patients who had three or more previous lines of
therapy, patients with liver metastases, and those who had not
responded to a PD-1/L1 inhibitor. Treatment-related adverse events
that occurred in 40 percent or more of patients were fatigue,
alopecia, rash, decreased appetite, taste distortion, and
peripheral neuropathy.
The data will be featured today in the official press program of
the American Society of Clinical Oncology (ASCO) Annual
Meeting and be presented as a Late-Breaking oral
presentation (Abstract #LBA4505) and have been submitted for
publication in a peer-reviewed journal.
Despite recent advances in treatment, approximately 80 percent
of people do not respond to PD-1/L1 inhibitors, which are the
standard of care after platinum-containing therapy has failed as an
initial treatment for advanced disease.[1],[2],[3] These
patients have few treatment options and new therapies are urgently
needed.
Enfortumab vedotin is an investigational antibody-drug conjugate
(ADC) that targets Nectin-4, a protein that is highly expressed in
urothelial cancers.[4],[5] Based on the results of the
EV-201 trial, the companies plan to submit a Biologics License
Application (BLA) for enfortumab vedotin to the U.S. Food and
Drug Administration (FDA) this year. Based on preliminary results
from the phase 1 EV-101 trial, the FDA granted enfortumab vedotin
Breakthrough Therapy designation for people with locally advanced
or metastatic urothelial cancer whose disease has progressed during
or following checkpoint inhibitor therapy.
"Outcomes for patients diagnosed with locally advanced or
metastatic urothelial cancer are generally poor, and treatment
options after initial chemotherapy and immunotherapy are very
limited," said Daniel P. Petrylak,
M.D., Professor of Medicine and of Urology, Yale Cancer Center, New
Haven. "These data have the potential to change the treatment
course of advanced urothelial cancer, and it is gratifying to see
these results for patients."
"Even with the recent introduction of new therapies, there
remains a need for continued innovation in the treatment of
urothelial cancer, and if approved, we hope to bring this potential
treatment to physicians and patients as quickly as possible," said
Andrew Krivoshik, M.D., Ph.D.,
Senior Vice President and Oncology Therapeutic Area Head at
Astellas.
"We are encouraged that enfortumab vedotin is the first novel
therapy to demonstrate substantial clinical activity in these
difficult-to-treat patients who currently have limited treatment
options," said Roger Dansey, M.D.,
Chief Medical Officer at Seattle Genetics.
A global, randomized phase 3 confirmatory clinical trial
(EV-301) is ongoing and is intended to support global
registrations. Another trial (EV-103) is underway to evaluate
enfortumab vedotin in earlier lines of treatment for patients with
locally advanced or metastatic urothelial cancer, including in
combination with pembrolizumab and/or platinum chemotherapy in
newly diagnosed patients as well as patients who progressed from
earlier-stage disease.
EV-201 Study Results
Efficacy
In the first cohort of the EV-201 study, 125 patients were treated
with enfortumab vedotin. The primary endpoint of confirmed
objective response rate (ORR) was 44 percent per blinded
independent central review (BICR) [(55/125; 95% CI:
35.1-53.2)]. The overall duration of response (DoR), a key
secondary endpoint, was 7.6 months (range 0.95-11.3+).
Most responses occurred within the first cycle of treatment, and
were observed across all pre-specified patient subgroups
irrespective of lines of therapy, response to prior PD-1/L1
inhibitor, or presence of liver metastases:
- Three or more prior therapies: 41 percent ORR (26/63)
- Non-responders to PD-1/L1 inhibitors: 41 percent ORR
(41/100)
- Liver metastases: 38 percent ORR (19/50)
Median overall survival (OS) was 11.7 months (95% CI:9.1-not
reached), and the median progression-free survival (PFS) was 5.8
months (95% CI:4.9-7.5).
Safety
- The most common treatment-related adverse events (AEs)
occurring in more than 40 percent of patients were fatigue (50
percent (62/125)); alopecia (49 percent (61/125)); rash (48 percent
(60/125)); decreased appetite (44 percent (55/125)); taste
distortion (40 percent (50/125)); and peripheral neuropathy (50
percent (63/125)).
- Most peripheral neuropathy (94 percent) and rash (75 percent)
were less than or equal to Grade 2 in severity. Hyperglycemia
occurred in 11 percent of patients (14/125).
- The most common severe AEs (defined as greater than or equal to
Grade 3) were: neutropenia – experienced by 8 percent of patients
(10/125); anemia in 7 percent of patients (9/125); and fatigue in 6
percent of patients (7/125). One death due to interstitial lung
disease occurred outside the safety-reporting period and was
confounded by prolonged high-dose steroid use and suspected
pneumonia.
About the EV-201 Trial
EV-201 is an ongoing
single-arm, pivotal phase 2 clinical trial of enfortumab vedotin in
patients with locally advanced or metastatic urothelial cancer who
have been previously treated with a PD-1/L1 inhibitor, including
those who have also been treated with a platinum-containing
chemotherapy (cohort 1) and those who have not received a
platinum-containing chemotherapy and who are ineligible for
cisplatin (cohort 2). EV-201 continues to enroll patients in
cohort 2. In cohort 1, 128 patients were enrolled at multiple
centers internationally.[6] The primary endpoint is confirmed
objective response rate per blinded independent central review.
Secondary endpoints include assessments of duration of response,
disease control rate, progression-free survival, overall survival,
safety and tolerability.
More information about enfortumab vedotin clinical trials can be
found at clinical trials.gov.
About Urothelial Cancer
Urothelial cancer is the most
common type of bladder cancer (90 percent of cases).[7] In 2018,
more than 82,000 people were diagnosed with bladder cancer in the
United States.[8] Globally, approximately 549,000 people were
diagnosed with bladder cancer last year, and there were
approximately 200,000 deaths worldwide.
About Enfortumab Vedotin
Enfortumab vedotin is
an investigational ADC composed of an anti-Nectin-4 monoclonal
antibody attached to a microtubule-disrupting agent, MMAE, using
Seattle Genetics' proprietary linker technology. Enfortumab vedotin
targets Nectin-4, a cell adhesion molecule that is expressed on
many solid tumors, and that has been identified as an ADC target by
Astellas.
The safety and efficacy of enfortumab vedotin are under
investigation and have not been established. There is no guarantee
that the agent will receive regulatory approval or become
commercially available for the uses being investigated.
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 Astellas and Seattle Genetics Collaboration
Seattle Genetics and Astellas are co-developing 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 Statement
Certain
statements made in this press release are forward looking, such as
those, among others, relating to the companies' plan to submit a
Biologics License Application (BLA) to the FDA in the near term
under FDA's Accelerated Approval program based on the results of
cohort 1 of the pivotal EV-201 trial, conduct of a comprehensive
clinical development program for enfortumab vedotin, which includes
an ongoing randomized phase 3 confirmatory trial (EV-301) intended
to support global registration in locally advanced or metastatic
urothelial cancer, and the therapeutic potential of enfortumab
vedotin; its possible safety, efficacy, and therapeutic uses;
and anticipated development activities including future clinical
trials and intended regulatory actions. 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 of delays in the submission of a
BLA to the FDA; that the data from EV-201 may not be sufficient to
support accelerated approval; and the inability to show sufficient
activity in EV-301 and subsequent clinical trials; the risk of
adverse events or safety signals; and the possibility of adverse
regulatory actions as enfortumab vedotin advances in clinical
trials even after promising results in earlier clinical trials.
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
March 31, 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.
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] Kim HS, Seo HK, Immune checkpoint inhibitors for urothelial
carcinoma. Investig Clin Urol 2018 Sep;59(5):285-296
[2] Alhalabi O, Shah AY, Lemke EA, Gao J. Current and Future
Landscape of Immune Checkpoint Inhibitors in Urothelial Cancer.
Oncology (Williston Park). 2019 Jan
17;33(1):11-8
[3] National Comprehensive Cancer Network. Bladder Cancer
(Version 3.2019).
http://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
[4] Vlachostergios P, Jakubowski C, Niaz J, et al. (2018).
Antibody-Drug Conjugates in Bladder Cancer. Bladder Cancer (Version
4.2018).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087439/pdf/blc-4-blc180169.pdf
[5] Astellas Pharma Global Development, Inc. Bladder Cancer
(2019).
https://bladdercancerjournal.com/study-escalating-doses-asg-22ce-given-monotherapy-subjects-metastatic-urothelial-cancer-and-other
[6] Data on file at Seattle Genetics
[7] American Society of Clinical Oncology. Bladder Cancer:
Introduction (05-2019).
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
[8] International Agency for Research on Cancer. Cancer tomorrow:
bladder. http://gco.iarc.fr/tomorrow.
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