SAN FRANCISCO, May 31, 2014 /PRNewswire/ -- Nektar Therapeutics
(NASDAQ: NKTR) announced today new data from an
investigator-sponsored Phase 2 study of NKTR-102 (etirinotecan
pegol) in patients with Avastin-refractory high-grade glioma
conducted at Stanford Cancer Institute under the direction of
Lawrence Recht, M.D., Professor of
Neurology and Neurosurgery, with co-investigator Seema Nagpal, M.D., Clinical Assistant Professor
of Neurology and Neurological Sciences, Stanford School of
Medicine.
"Patients with Avastin-refractory high-grade glioma currently
have little to no treatment options to help them manage their
disease," said Dr. Recht. "Patients progress rapidly once
resistance develops, objective responses are rarely seen. In this
study we saw three patients – 15%, all with glioblastoma - with
confirmed partial responses on single-agent NKTR-102 according to
RANO criteria and an additional eight patients – 40% -- who had
stable disease as a best response."
The trial enrolled 20 patients with high-grade glioma from
August 2012 to May
2013. Patients had a median KPS of 70 and had received a
median of three lines of prior therapy, including recurrence
following treatment with Avastin. Avastin-refractory was defined as
progression by RANO criteria within 60 days of prior Avastin
(bevacizumab) treatment. Ninety percent of patients in the
trial had glioblastoma. Patients received a median of three
cycles (1-22) of NKTR-102 once every three weeks as
monotherapy. Six-week progression-free survival in at least
25% of the patients was needed to reject the null hypothesis for
the primary endpoint.
Study Results
The primary endpoint was met and
exceeded with fifty-five percent (95% CI: 31%-75%) of patients in
the study achieving six-week progression-free survival. Response
and disease progression were assessed by RANO criteria in the
trial. Three patients, or 15%, achieved partial responses with
NKTR-102 monotherapy with maximum percent reductions in tumor area
of 86%, 72%, and 59%. An additional eight patients, or 40%,
achieved stable disease as best response. Two of the three patients
with RANO responses experienced a long duration of response of 14
and 20 months. Secondary endpoints include median progression-free
survival (2.2 months), median survival from time of first NKTR-102
infusion (4.5 months) and median overall survival from date of
pathologic diagnosis or confirmation of high-grade glioma (17.1
months). NKTR-102 monotherapy was well-tolerated in patients with
Avastin-refractory high-grade glioma with low toxicity in spite of
being heavily pre-treated and neurologically symptomatic. Only one
patient (5%) had Grade 3 toxicity (diarrhea with dehydration)
attributable to NKTR-102 as a result of not taking anti-diarrheal
medication. Hematologic toxicity was mild. As of May 31, 2014, there is one patient in the study
who is continuing on NKTR-102 monotherapy.
"Though participants in this trial were heavily pre-treated and
more neurologically symptomatic than many clinical trial patients,
we observed low toxicity with three partial responses," said Dr.
Nagpal. "In addition, two of the three patients with responses
experienced a long duration of response of 14 and 20 months,
respectively. These results warrant further investigation of
NKTR-102 in high-grade glioma, including glioblastoma as
single-agent and in combination with bevacizumab, which could
theoretically enhance retention of NKTR-102 in the tumor."
The ASCO 2014 data presentation can be accessed at the link
below:
http://www.nektar.com/pdf/pipeline/NKTR-102/NKTR-102_ASCO_Poster_2014.pdf
About High-Grade Gliomas
High-grade gliomas, including
anaplastic astrocytomas, anaplastic oligodendrogliomas, and
glioblastomas, are the most common and most aggressive primary
brain tumors. Recurrence after initial therapy with temozolomide
and radiation is nearly universal. Since May
2009, the majority of patients in the U.S. with an initial
recurrence of high-grade glioma receive bevacizumab. Avastin
has initial response rates from 32-62%1, however, the
response is short-lived and nearly 100% of patients eventually
progress. Patients with high-grade gliomas who have progressed
through bevacizumab represent a population in dire need of new
therapies.
About NKTR-102 (etirinotecan pegol)
NKTR-102, a novel topoisomerase I inhibitor, is believed to
penetrate the vasculature of the tumor environment more readily
than normal vasculature, increasing the concentration of active
drug within tumor tissue to enhance anti-tumor activity. The unique
pharmacokinetic profile of NKTR-102 provides continuous exposure of
active drug throughout the entire chemotherapy cycle, with reduced
peak exposures that can be associated with toxicities. NKTR-102 is
currently being evaluated in a pivotal Phase 3 clinical study in
patients with advanced breast cancer (the BEACON study). In
November 2012, NKTR-102 was
designated a Fast Track development program by the U.S. FDA for the
treatment of patients with locally recurrent or metastatic breast
cancer progressing after treatment with ATC. Additional
investigator-sponsored studies at Roswell Park Cancer Institute and
University of Pennsylvania Abramson
Cancer Center are ongoing to evaluate NKTR-102 in patients with
small cell lung cancer and non-small cell lung cancer,
respectively.
About Nektar
Nektar Therapeutics (NASDAQ: NKTR) is a
biopharmaceutical company developing novel therapeutics based on
its PEGylation and advanced polymer conjugation technology
platforms. Nektar has a robust R&D pipeline of potentially
high-value therapeutics in pain, oncology and other therapeutic
areas. In the area of pain, Nektar has an exclusive worldwide
license agreement with AstraZeneca for naloxegol (NKTR-118), an
investigational drug candidate, which has been filed for regulatory
approvals in the U.S., Europe and
Canada as a once- daily, oral
tablet for the treatment of opioid-induced constipation. This
agreement also includes NKTR-119, an earlier stage development
program that is a co-formulation of naloxegol and an opioid.
NKTR-181, a novel mu-opioid analgesic molecule for chronic pain
conditions, has completed Phase 2 development in osteoarthritis
patients with chronic knee pain. NKTR-171, a new sodium channel
blocker being developed as an oral therapy for the treatment of
peripheral neuropathic pain, is in Phase 1 clinical development. In
oncology, etirinotecan pegol (NKTR-102) is being evaluated in a
Phase 3 clinical study (the BEACON study) for the treatment of
metastatic breast cancer and is also in Phase 2 studies for the
treatment of ovarian, colorectal, lung and brain cancers. 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.
Additional development-stage products that leverage Nektar's
proprietary technology platform include Baxter's BAX 855, a long-acting PEGylated
rFVIII program, which is in Phase 3 clinical development for
patients with hemophilia A.
Nektar's technology has enabled eight approved products in the
U.S. or Europe through
partnerships with leading biopharmaceutical companies, including
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.
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," "could,"
"potential," "may" and similar references to future periods.
Examples of forward-looking statements include those statements
regarding the therapeutic potential of etirinotecan pegol and the
potential of certain of our other drug candidates and those of our
collaboration partners. Forward-looking statements are neither
historical facts nor assurances of future performance. Instead,
they are based only on our current beliefs, expectations,
observations and assumptions regarding the potential of our drug
candidates and our technology. 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) etirinotecan
pegol is still in clinical development and the risk of failure is
high and can unexpectedly occur at any time prior to regulatory
approval for numerous reasons including safety and efficacy
findings from the ongoing BEACON clinical study program; (ii) the
timing of the commencement or end of clinical trials, target
timeframe for the availability of clinical results, and the
successful commercial launch of our drug candidates may be delayed
or unsuccessful due to manufacturing challenges, changing standards
of care, regulatory delay, evolving regulatory requirements,
clinical trial design, clinical outcomes, competitive factors, or
delay or failure in ultimately obtaining regulatory approval in one
or more important markets; (iii) scientific discovery of new
medical breakthroughs is an inherently uncertain process and the
future success of the application of our technology platform to
potential new drug candidates such as etirinotecan pegol is
therefore very uncertain and unpredictable and could unexpectedly
fail at any time; (iv) patents may not issue from our patent
applications for etirinotecan pegol, patents that have issued may
not be enforceable, or additional intellectual property licenses
from third parties may be required; and (v) the outcome of any
existing or future intellectual property or other litigation
related to our proprietary drug candidates including etirinotecan
pegol. Other important risks and uncertainties are detailed in our
reports and other filings with the Securities and Exchange
Commission ("SEC"), including without limitation, those risks and
uncertainties set forth in our most recent quarterly report on Form
10-Q filed with the SEC on May 8,
2014. 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.
Nektar Investor Inquiries:
Jennifer
Ruddock/Nektar 415-482-5585
Susan
Noonan 212-966-3650
Nektar Media Inquiries:
Karin
Bauer/MSL 415-527-8912
1. Chamberlain MC. Bevacizumab for
recurrent malignant gliomas: efficacy, toxicity, and patterns of
recurrence. Neurology. 2009; 72(8): 772-3; author reply 3-4.
DEFINITIONS:
RANO: Revised Assessment in Neuro-Oncology (RANO) criteria is used
for assessing disease progression and treatment response in
glioblastoma multiforme (GBM)
KPS: Karnofsky Performance Status Scale: A standard way of
measuring the ability of cancer patients to perform ordinary tasks.
The Karnofsky Performance scores range from 0 to 100. A higher
score means the patient is better able to carry out daily
activities. KPS may be used to determine a patient's prognosis, to
measure changes in a patient's ability to function, or to decide if
a patient could be included in a clinical trial.
Avastin is a registered trademark of Genentech.
SOURCE Nektar Therapeutics