SAN FRANCISCO, June 19, 2014 /PRNewswire/ -- Nektar Therapeutics
(NASDAQ:NKTR) reported that partner AstraZeneca today announced
that the New England Journal of Medicine (NEJM) has
published results of two pivotal Phase III studies – KODIAC-4 and
KODIAC-5 of naloxegol, an investigational treatment for
opioid-induced constipation (OIC).
Opioids play an important role in chronic pain relief by binding
to mu-receptors in the brain, but they also bind to mu-receptors in
the bowel. That is why patients taking opioids for chronic
pain can develop OIC. In fact, the incidence of OIC varies and has
been reported as high as 81%* in patients taking opioids.
Naloxegol, which has the potential to be the first FDA approved
once-daily oral treatment for patients with OIC, is a
peripherally-acting mu-opioid receptor antagonist (PAMORA) studied
in adult patients with chronic non-cancer pain experiencing
OIC.
**Primary endpoint data from the KODIAC-4 and -5 studies showed
that more OIC patients treated with naloxegol 25 mg had a
consistent response of increased spontaneous bowel movements (SBMs)
through 12 weeks of treatment compared to placebo [44% vs. 29%
(p=0.001 KODIAC-4) and 40% vs. 29% (p=0.021 KODIAC-5)]. The 12.5 mg
dose in KODIAC-5 did not show statistical significance for the
primary endpoint.
The 25 mg dose also demonstrated a higher response rate through
12 weeks of treatment compared to placebo in patients with laxative
inadequate response (LIR), a secondary endpoint. Results for an
additional secondary endpoint showed that patients taking naloxegol
25 mg in the KODIAC-4 and KODIAC-5 studies were likely to have
a first post-dose spontaneous bowel movement 25-30 hours sooner
than placebo, respectively (median six and 12 hours for naloxegol
25 mg compared to 36 and 37 hours for placebo, in studies
KODIAC-4 and -5, respectively).
"An estimated 235 million prescriptions for opioids are written
in the US each year, of which 20% are for chronic pain. For
patients taking prescription opioids for chronic pain, constipation
is one of the most common and bothersome side effects, and these
patients can experience sub-optimal relief from laxatives," said
William Chey, MD, AGAF, FACG, FACP,
Professor of Medicine at the University of
Michigan Health System. "These results demonstrated the
potential for naloxegol, if approved, to be a new treatment option
as the studies showed rapid and sustained improvement for these
patients, without compromising their pain management over the
course of the trials."
The Phase III studies, KODIAC-4 (n=652) and KODIAC-5 (n=700),
were 12-week, multicenter, randomised, double blind,
placebo-controlled pivotal trials that evaluated 12.5 mg and 25 mg
doses of naloxegol, administered once-daily.
Additional results from the KODIAC-4 and KODIAC -5 clinical
trials published in NEJM included:
- The number of SBMs per week increased with naloxegol 25 mg
treatment over 12 weeks, with both studies showing an improvement
in treatment effect versus placebo
- Improvements in straining, stool consistency, and frequency of
days with complete SBMs were observed with naloxegol 25 mg (both
studies)
- The most commonly reported adverse effects with naloxegol were
gastrointestinal in origin (abdominal pain, diarrhea, nausea,
vomiting, flatulence) and appeared to be dose-ordered, occurring
more commonly in the 25 mg group. Most adverse events were mild to
moderate in severity and occurred shortly after initiation of
naloxegol
- There was 1 major adverse cardiovascular event (MACE) in the 25
mg treatment arm, 1 in the 12.5 mg treatment arm and 2 in the
placebo arm
A New Drug Application (NDA) for naloxegol was accepted by the
US Food and Drug Administration on 19
November 2013. MOVANTIKTM is the proposed
proprietary name for naloxegol. On June
11-12, 2014, the FDA convened the Anesthetic Analgesic Drug
Products Advisory Committee (AADPAC) to review the class of
peripherally acting opioid receptor antagonists. The Committee
voted that the FDA should not require cardiovascular outcomes
trials for the PAMORA class of drugs which includes MOVANTIK.
Following a clarification of the vote, the majority of the
Committee suggested continued post-approval data collection for
cardiovascular safety. The Prescription Drug User Fee Act (PDUFA)
date set by the FDA for MOVANTIK is September 16, 2014.
MOVANTIK is also under regulatory review with health agencies in
the European Union and Canada.
About naloxegol
Naloxegol is an investigational
peripherally-acting mu-opioid receptor antagonist (PAMORA), which
has been specifically designed for the treatment of opioid-induced
constipation, a condition caused by prescription opioid pain
medicines. In the Phase III clinical studies, naloxegol was
administered as a once-daily tablet and is designed to block the
binding of opioids to the opioid receptors in the gastrointestinal
(GI) tract without impacting the opioid receptors in the brain.
Naloxegol is part of the exclusive worldwide license agreement
announced in September 2009, between
AstraZeneca and Nektar Therapeutics. Naloxegol was developed using
Nektar's proprietary oral small molecule polymer conjugate
technology.
About Opioid-Induced Constipation
Opioids play an
important role in chronic pain relief by binding mu-receptors in
the brain. But they also bind mu-receptors in the
bowel. That is why patients taking opioids for chronic pain
can develop opioid-induced constipation (OIC). In fact, the
incidence of OIC varies and has been reported as high as 81%* in
patients taking opioids.
*Published estimates of the incidence of OIC in patients
receiving opioids for chronic pain vary due to differences in the
studies conducted (eg, study design, definition of constipation,
opioids used). Meta-analyses of randomized controlled trials
suggest that 15%–41% of these patients develop OIC, while
observational and survey based studies suggest that 37%–81% develop
OIC.
**The primary endpoint in both trials was percentage of OIC
responders, versus placebo, over 12 weeks of treatment.
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,"
"may," "will" and similar references to future periods. Examples of
forward-looking statements include, among others, statements we
make regarding the therapeutic potential for MOVANTIKTM
(naloxegol), the regulatory process and outcomes for MOVANTIK, 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 voting and
recommendations from the AADPAC are advisory only and not binding
on the FDA; (ii) upcoming FDA determinations made in the MOVANTIKTM
new drug application review process will have a significant impact
on the Company's financial position based on significant regulatory
and launch milestone opportunities and a potential repayment
obligation by the Company to AstraZeneca as described in our most
recent Quarterly Report on Form 10-Q filed with the SEC on
May 8, 2014 (the "Form 10-Q") and the
Current Report on Form 8-K filed with the SEC on August 8, 2013; (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) the timing of the commencement or end of clinical trials and
the commercial launch of our drug candidates may be delayed or
unsuccessful due to regulatory delays, slower than anticipated
patient enrollment, manufacturing challenges, changing standards of
care, 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; (v) 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; (vi)
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 is therefore
highly uncertain and unpredictable and one or more research and
development programs could fail; and (vii) certain other important
risks and uncertainties set forth in our Form 10-Q. 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.
Nektar Investor
Inquiries:
|
|
Jennifer
Ruddock/Nektar
|
415-482-5585
|
Susan
Noonan
|
212-966-3650
|
Nektar Media
Inquiries:
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Karin
Bauer/MSL
|
415-527-8912
|
SOURCE Nektar Therapeutics