SAN FRANCISCO, March 17, 2015 /PRNewswire/ -- Nektar
Therapeutics (NASDAQ: NKTR) today announced topline results from
its Phase 3 BEACON study evaluating single-agent NKTR-102 in
patients with advanced breast cancer. BEACON compared NKTR-102 to
an active control arm comprised of a single chemotherapy agent of
physician's choice (TPC) in patients who were heavily pre-treated
with a median of three prior therapies for metastatic
disease. In a topline analysis of 852 patients from the
trial, NKTR-102 provided a 2.1 month improvement in median overall
survival (OS) over TPC (12.4 months for patients receiving NKTR-102
compared to 10.3 months for patients receiving TPC). Based on
a stratified log-rank analysis, the primary endpoint measuring the
Hazard Ratio (HR) for survival in the NKTR-102 group compared to
the active control arm was 0.87 with a p-value of 0.08, which did
not achieve statistical significance.
In a pre-specified subgroup of patients with a history of brain
metastases, NKTR-102 showed an improvement of 5.2 months in
median OS (10.0 months compared to 4.8 months, n=67, HR 0.51,
p-value <0.01). The proportion of patients with brain
metastases with 12-month survival was 44.4% in the NKTR-102 arm as
compared to 19.4% in the control arm.
In a pre-specified subgroup of patients with baseline liver
metastases at study entry, NKTR-102 showed an improvement of 2.6
months in median OS (10.9 months versus 8.3 months, n=456, HR 0.73,
p-value <0.002). In these patients with baseline liver
metastases, the proportion of patients with 12-month survival was
46.9% in the NKTR-102 arm as compared to 33.3% in the control
arm.
Breast cancer is the second leading cause of cancer related
death among women, according to the National Cancer
Institute. This year, an estimated 207,000 women will be
diagnosed with breast cancer, and over 39,000 women will die from
the disease in the U.S. Brain metastases are diagnosed in 30%
of patients with advanced breast cancer.1 Liver
metastases develop in approximately half of all women with
metastatic breast cancer and are typically associated with advanced
disease and poor outcome.2
"In BEACON, NKTR-102 provided a clinically meaningful benefit
with a greater than two month survival advantage in these
late-stage breast cancer patients, many who were refractory to
existing therapies," said Dr. Cortes. "NKTR-102 exhibited a lower
rate of high grade adverse events including a reduced rate of
neutropenia as compared to active control, which dramatically
decreased the need for growth factor support in the NKTR-102 arm of
the study. Of particular significance, median survival in
patients with brain metastases was more than double on NKTR-102 and
the 12-month survival rate for this sub-group was impressive at 44%
compared to 19% with other active agents."
Dr. Edith Perez, Deputy Director
of the Mayo Clinic Cancer Center and Dr. Javier Cortes, Director of the Breast Cancer
Program at Vall d'Hebron University Hospital in Spain,
served as co-principal investigators of the global, multi-center
study. BEACON enrolled 852 patients with advanced breast
cancer whose disease had progressed following treatment with
anthracycline, taxane and capecitabine (ATC).
"Given the frequency of cross-resistance and overlapping
toxicities observed with many available agents, NKTR-102 would
offer a new mechanism of action for physicians and patients in the
fight against advanced breast cancer," said Dr. Joyce O'Shaughnessy, a lead BEACON investigator
and steering committee member in the
United States and Chair, Breast Cancer Research, The US
Oncology Network and the Baylor Sammons Cancer Center, Texas Oncology, Dallas, Texas. "The results in the subgroups
of patients with both liver and brain metastases are
noteworthy because NKTR-102 is designed to enhance concentration of
its active metabolite in highly vascular tumor environments. From a
clinician's perspective, the combination of NKTR-102's clinical
benefit and improved tolerability supports its value as a potential
new treatment option in late stage breast cancer."
Secondary endpoints in the BEACON study included objective
response rate (ORR) and progression-free survival (PFS), which did
not achieve statistical significance in the study.
The incidence of Grade 3 and higher adverse events (AEs) was
lower in the NKTR-102 arm (48%) compared to the TPC arm
(63%). The most common Grade 3 and above AEs observed with
NKTR-102 were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%)
and fatigue (4.5%). There was no Grade 4 diarrhea reported
with NKTR-102 in the trial. The most common Grade 3 and above AEs
observed with TPC were neutropenia (30.8%), anemia (4.7%), and
dyspnea (4.4%). Severe neuropathy (G3 or higher) was seen in
3.7% of patients on TPC versus 0.5% of patients in the NKTR-102
arm. Rates of G1/G2 alopecia in the NKTR-102 arm were also
lower (10%) than in the TPC arm (23%).
"It is clear from our BEACON study that NKTR-102 has potential
as an important anti-cancer agent when compared to the best
available treatment options today for women with advanced breast
cancer," said Howard W. Robin,
president and chief executive officer of Nektar Therapeutics.
"Given the significant need for new drugs to treat patients with
this devastating disease, we will be exploring potential paths
forward for NKTR-102 in metastatic breast cancer with regulatory
agencies."
NKTR-102 was designed to be the first topoisomerase I
inhibitor with a novel molecular structure that concentrates the
drug in vascularized tumors and extends its circulation time in the
plasma. In 2012, the FDA designated NKTR-102 as a Fast Track
development program for the treatment of patients with locally
recurrent or metastatic breast cancer progressing after treatment
with ATC.
Nektar will continue to review and analyze the data
from the BEACON study. Data from the BEACON study will be
submitted for presentation at an upcoming medical meeting.
Conference Call, Slide Presentation and Webcast
Information
Nektar will host a conference call and
webcast slide presentation today, March 17, 2015,
at 4:45 PM Eastern Time. The call can be accessed by
dialing (877) 881-2183 (U.S.) or (970)
315-0453 (international), and entering passcode 9310762. To
access the live webcast, or the subsequent archived recording,
visit the Investor Relations section of the Nektar website at
www.nektar.com. The webcast will be available for replay on
Nektar's website through March 31,
2015.
About the BEACON Study Design
The open-label,
randomized, multicenter study enrolled 852 women with locally
recurrent or metastatic breast cancer who previously had been
treated with ATC and had progressed following treatment. The study
was conducted at 139 sites worldwide including in North America, Europe and the Republic of Korea. Nearly half
of the patients enrolled in BEACON were located in North America. Patients were randomized on a
1:1 basis to receive 145 mg/m2 of single-agent NKTR-102 once every
three weeks or a single agent of the physician's choice, including
ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane.
Randomization was stratified by geographic region, prior use of
eribulin and receptor status.
The primary endpoint of the BEACON study was overall survival;
key secondary endpoints included objective tumor response rates and
progression-free survival. The study also evaluated specific
biomarker data to assess correlation with efficacy and safety
outcomes.
About NKTR-102
NKTR-102 is the first long-acting
topoisomerase I inhibitor with an extended half-life and a
unique structure that is designed to concentrate the drug in
tumors. In patients, NKTR-102 leads to greatly prolonged plasma
SN38 exposure compared with irinotecan (elimination half-life of 50
days compared with 2 days) yet peak SN38 concentrations are at
least 5- to 10-times less, which may also result in a favorable
tolerability profile.
About Metastatic Breast Cancer
Breast cancer is the
most frequently diagnosed cancer and is the leading cause of cancer
death among women worldwide.i More than 1.6 million new
cases of breast cancer were diagnosed among women around the world
in 2010.ii Approximately 425,000 women around the world
died from the disease in 2010.iii There are
approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year.iv Metastatic
breast cancer refers to cancer that has spread from the breast to
distant sites in the body.
Anthracyclines and taxanes (AT) are the most active and widely
used chemotherapeutic agents for breast cancer. However, the
increased use of these agents at an early stage of disease often
renders tumors resistant to these drugs by the time the disease
recurs, thereby reducing the number of treatment options for
metastatic disease. Drugs used to treat patients who progress
following AT treatment can have response rates as high as 20 to 30
percent. However, resistance develops rapidly and new agents with
different mechanisms of action, such as topoisomerase I inhibitors,
are needed to allow novel ways to overcome the problem of drug
resistance.v There are currently no FDA-approved
topoisomerase I inhibitors to treat breast cancer.
About Nektar
Nektar Therapeutics has a robust R&D
pipeline in pain, oncology, hemophilia and other therapeutic areas.
In the area of pain, Nektar has an exclusive worldwide license
agreement with AstraZeneca for MOVANTIK™ (naloxegol), the first
FDA-approved once-daily oral peripherally-acting mu-opioid receptor
antagonist (PAMORA) medication for the treatment of opioid-induced
constipation (OIC), in adult patients with chronic, non-cancer
pain. The product is also approved in the European Union as
MOVENTIG® and is indicated for adult patients with OIC who have had
an inadequate response to laxatives. The AstraZeneca agreement also
includes NKTR-119, an earlier stage development program that is a
co-formulation of MOVANTIK™ and an opioid. NKTR-181, a wholly-owned
mu-opioid analgesic molecule for chronic pain conditions, is in
Phase 3 development. NKTR-171, a wholly-owned new sodium channel
blocker being developed as an oral therapy for the treatment of
peripheral neuropathic pain, is in Phase 1 clinical development. In
hemophilia, BAX 855, a longer-acting PEGylated Factor VIII
therapeutic is in Phase 3 development conducted by partner
Baxter. A BLA for BAX 855 was
filed by Baxter to the US FDA in
December, 2014 and is currently under review. In anti-infectives,
Amikacin Inhale is in Phase 3 studies conducted by Bayer Healthcare
as an adjunctive treatment for intubated and mechanically
ventilated patients with Gram-negative pneumonia.
Nektar's technology has enabled nine approved products in the
U.S. or Europe through
partnerships with leading biopharmaceutical companies, including
AstraZeneca's MOVANTIK™, UCB's Cimzia® for Crohn's disease and
rheumatoid arthritis, Roche's PEGASYS® for hepatitis C and Amgen's
Neulasta® for neutropenia.
Nektar is headquartered in San
Francisco, California, with additional operations in
Huntsville, Alabama and
Hyderabad, India. Further
information about the company and its drug development programs and
capabilities may be found online at http://www.nektar.com.
MOVANTIK™ is a trademark of the AstraZeneca group of
companies.
Cautionary Note Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements can be identified by words such as:
"anticipate," "intend," "plan," "expect," "believe," "should,"
"may," "will" and similar references to future periods. Examples of
forward-looking statements include, among others, statements we
make regarding the potential of NKTR-102 and the value and
potential of our technology and research and development pipeline.
Forward-looking statements are neither historical facts nor
assurances of future performance. Instead, they are based only on
our current beliefs, expectations and assumptions regarding the
future of our business, future plans and strategies, anticipated
events and trends, the economy and other future conditions. Because
forward-looking statements relate to the future, they are subject
to inherent uncertainties, risks and changes in circumstances that
are difficult to predict and many of which are outside of our
control. Our actual results may differ materially from those
indicated in the forward-looking statements. Therefore, you should
not rely on any of these forward-looking statements. Important
factors that could cause our actual results to differ materially
from those indicated in the forward-looking statements include,
among others, (i) the FDA and European Medicines Agency rarely
approve drugs on the basis of studies that do not achieve
statistical significance on the primary endpoint; (ii) while data
from certain pre-specified subgroups in the BEACON study was
positive, the study did not achieve statistical significance for
its primary endpoint and secondary endpoints; (iii) our drug
candidates and those of our collaboration partners are in various
stages of clinical development and the risk of failure is high and
can unexpectedly occur at any stage prior to regulatory approval
for numerous reasons including safety and efficacy findings even
after positive findings in previous preclinical and clinical
studies; (iv) acceptance, review and approval decisions for new
drug applications by health authorities is an uncertain and
evolving process and health authorities retain significant
discretion at all stages of the regulatory review and approval
decision process; (v) patents may not issue from our patent
applications for our drug candidates, patents that have issued may
not be enforceable, or additional intellectual property licenses
from third parties may be required; and (vi) the outcome of any
existing or future intellectual property or other litigation
related to our drug candidates and those of our collaboration
partners. Other important risks and uncertainties
are set forth in our Annual Report on Form 10-K filed with the
Securities and Exchange Commission on February 26, 2015. Any forward-looking statement
made by us in this press release is based only on information
currently available to us and speaks only as of the date on which
it is made. We undertake no obligation to update any
forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information,
future developments or otherwise.
Contact:
Investors
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Media
Nadia Hasan of WCG
212-257-6738
1 Cancer Metastases Review, 2007
2 Selzner et. al., Surgery 2000; 127 (4): (383-389).
i American Cancer Society, Global Cancer Facts
& Figures 2nd edition.
ii Institute for Health Metrics and Evaluation,
University of Washington, The Challenge
Ahead: Progress and Setbacks in Breast and Cervical Cancer,
September 2011. Also see: Breast and
cervical cancer in 187 countries between 1980 and 2010: a
systematic analysis. www.thelancet.com September 15, 2011.
iii Institute for Health Metrics and Evaluation,
University of Washington, The Challenge
Ahead: Progress and Setbacks in Breast and Cervical Cancer,
September 2011. Also see: Breast and
cervical cancer in 187 countries between 1980 and 2010: a
systematic analysis. www.thelancet.com September 15, 2011.
iv American Cancer Society, 2009 Global Cancer Facts and
Figures Report.
v Moreno-Aspitia and Perez, Mayo
Clin Proc. 2009; 84(6):533-545.
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