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Seattle Genetics and Astellas Announce Antibody-Drug Conjugate Enfortumab Vedotin Produced Tumor Response Rate of 44 Percent in Patients with Most Common Type of Advanced Urothelial (Bladder) Cancer

June 3, 2019 Off By BusinessWire

–First Investigational Therapy in a Pivotal Trial to Address Unmet
Need for Patients with Advanced Urothelial Cancer After Treatment with
Platinum Chemotherapy and a PD-1 or PD-L1 Inhibitor-

-Data Featured in Official Press Program and Presented in
Late-Breaking Oral Session Today at 2019 ASCO Annual Meeting-

BOTHELL, Wash. & TOKYO–(BUSINESS WIRE)–Seattle
Genetics, Inc. (Nasdaq:SGEN) and Astellas
Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D.,
“Astellas”) 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.”

“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.

“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.

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.

Contacts

Seattle Genetics Contacts:
For Media
Monique
Greer
Vice President, Corporate Communications
(425) 527-4641
[email protected]

For Investors
Peggy Pinkston
Vice President, Investor
Relations
(425) 527-4160
[email protected]

Astellas Contacts:
For Media
Marjorie Moeling
Director,
Corporate Affairs
(224) 205-5205
[email protected]

For Investors
Shin Okubo
Executive Director, Investor
Relations
+81-3-3244-3202
[email protected]