SAN FRANCISCO, March 20, 2017 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced positive results from
the SUMMIT-07 Phase 3 efficacy study of NKTR-181, a first-in-class
opioid analgesic. NKTR-181 is a new chemical entity (NCE)
that is the first full mu-opioid agonist molecule designed to
provide potent pain relief without the high levels of euphoria that
can lead to abuse and addiction with standard
opioids.1 The U.S. Food and Drug Administration
(FDA) has granted the investigational medicine NKTR-181 Fast Track
designation for the treatment of moderate to severe chronic
pain.
"The data from this efficacy study are extremely important
because they demonstrate that NKTR-181 produces strong analgesia in
patients suffering from chronic pain while NKTR-181 has also
demonstrated significantly lower abuse potential than oxycodone in
a human abuse potential study," said clinical investigator
Martin Hale, M.D., medical director
of Gold Coast Research. "While standard opioid analgesics,
including abuse-deterrent formulations, have been the most
effective way to treat chronic pain, they are associated with
serious safety concerns and many opioid-naïve patients fear taking
them because of the potential for abuse and addiction. The
data for NKTR-181 suggest that it is a transformational pain
medicine that could fundamentally change how we treat patients
with chronic pain conditions."
The SUMMIT-07 study compared twice-daily dosing of NKTR-181
tablets to placebo in the treatment of over 600 patients with
moderate to severe chronic low back pain who were new to opioid
therapy (opioid-naïve). The clinical trial met the primary efficacy
endpoint of the study in demonstrating significantly improved
chronic back pain relief with NKTR-181 compared to placebo
(p=0.0019). Key secondary endpoints of the study were also met with
high statistical significance.
Pain is one of the most common reasons people seek medical
treatment.2 Low back pain is the second most common
cause of disability for adults in the U.S. 3
Approximately 149 million work days are lost every year because of
low back pain, with total costs estimated to be $100 to 200 billion a year (of which two-thirds
is due to lost wages and lower productivity).4 A study
published in the American Pain Society's The Journal of Pain in
October 2014 estimated that 19
percent of the U.S. population, or 39 million people, suffer from
some type of persistent pain.5
The Phase 3 SUMMIT-07 study used an enriched-enrollment
randomized withdrawal (EERW) trial design in patients with moderate
to severe chronic low back pain. The trial included an open-label
titration period in which patients were titrated to a tolerated,
effective dose of NKTR-181 (100 mg to 400 mg twice-daily).
Following this open-label titration period, patients entered a
double-blind, placebo-controlled treatment period in which they
were randomized 1:1 to either continue to receive the tolerated,
effective dose of NKTR-181 or to receive matching placebo (i.e.
active drug was withdrawn) for a period of 12 weeks.
During the open-label titration period of the trial in which
patients were titrated to a tolerated, effective dose of NKTR-181,
average pain scores dropped by 65% (from 6.73 at screening to 2.32
at randomization, n=610).
The primary endpoint of the study was mean change in the weekly
average pain score in the double-blind randomized treatment period
from baseline (end of open-label titration period) to week 12 (end
of double-blind randomized treatment period).
Primary and key sensitivity analyses:
- During the double-blind randomized treatment period of the
trial, average pain scores increased more in the placebo arm versus
NKTR-181 at week 12 from randomization baseline (1.46, placebo
versus 0.92, NKTR-181, p=0.0019, n=610).
- 83% of patients completed the 12-week double-blind randomized
treatment period and for these study completers, average pain
scores increased more in the placebo arm versus NKTR-181 at week 12
from baseline (1.25, placebo versus 0.56, NKTR-181, p<0.0001,
n=504).
Key secondary endpoints:
- A statistically significant proportion of patients on NKTR-181
experienced pain reductions greater than 30% compared to placebo
(71.2% versus 57.1%; p=0.0003).
- A statistically significant proportion of patients on NKTR-181
experienced pain reductions greater than 50% compared to placebo
(51.1% versus 37.9%; p=0.001).
- A statistically significant proportion of patients on NKTR-181
reported their general overall status and quality of life as
"improved" or "very much improved" compared to placebo as assessed
by the Patient's Global Impression of Change (PGIC) of pain
medication questionnaire (51.5% versus 33.2%;
p<0.0001).
The study also demonstrated that NKTR-181 had a favorable safety
profile and was well tolerated. During the double-blind randomized
treatment period, the most commonly reported adverse events for
patients (>5%) were nausea (10.4%) and constipation (8.7%) in
the NKTR-181 arm as compared to nausea (6.0%) and constipation
(3.0%) in the placebo arm.
Patients randomized to NKTR-181 as compared to placebo reported
more favorable sleep outcomes as measured by the validated Medical
Outcomes Study (MOS) Sleep Scale, which captures debilitating
aspects of sleep most strongly associated with chronic pain.
Patients reported better overall quality of sleep with less sleep
problems on NKTR-181 versus placebo. There were no differences in
daytime sleepiness on NKTR-181 versus placebo.
Full data from the SUMMIT-07 study will be presented at a
medical meeting in the second half of 2017.
"As a new molecule, NKTR-181 has a highly differentiated profile
with the potential to be one of the most important advancements in
pain medicine," said Howard W.
Robin, President and CEO of Nektar Therapeutics. "Given the
seriousness of the current opioid epidemic in the U.S. and the
significant number of people battling chronic pain, we are
committed to bringing this new molecule to patients and physicians
as quickly as possible."
In March 2017, results from a
separate human abuse potential trial of NKTR-181 were published in
the American Academy of Pain Medicine's journal of Pain
Medicine. The human abuse potential
study assessed the relative abuse potential of a range of
therapeutic doses of NKTR-181 (100 mg to 400 mg), the same dose
range evaluated in the Phase 3 SUMMIT-07 efficacy trial. All
doses of NKTR-181 tested for abuse potential were rated
similarly to placebo in "drug liking" and "feeling high" scores and
had highly statistically significant lower "drug liking" scores and
reduced "feeling high" scores as compared to 40 mg oxycodone (p
< 0.0001). In addition, all doses of NKTR-181 also
scored lower on sleepiness when compared to 40 mg oxycodone (p <
0.0001).
"It is clear that there is a pressing societal need for better
and safer analgesics," said Dr. Jack
Henningfield, Ph.D., Adjunct Professor of Behavioral Biology
in the Department of Psychiatry and Behavioral Sciences at the
Johns Hopkins University School of
Medicine and Head of Health Policy and Abuse Liability at
Pinney & Associates in Bethesda,
MD. "In the human abuse potential study, even the highest
analgesic dose of NKTR-181 was barely distinguishable from placebo
with respect to both drug-liking and feeling high and these effects
were modest compared to those produced by oxycodone.
Drug-liking and feeling high are two of the most important metrics
that help us understand the abuse potential of a medicine.
Importantly, as NKTR-181 is a new chemical entity, the properties
of NKTR-181 are inherent to its molecular structure and independent
of any abuse-deterrent formulation. Today's reported efficacy
and safety results, along with the human abuse potential data
published this past week in Pain Medicine, suggest NKTR-181 may be
a major advance towards safer opioid therapy for the treatment of
moderate to severe chronic pain."
Conference Call and Webcast Information
Nektar will
host a conference call and webcast presentation today, March 20, 2017, at 8:45
a.m. Eastern Daylight Time to discuss the study results. The
call can be accessed by dialing (877) 881-2183 (U.S.) or (970)
315-0453 (international), and entering passcode 89288091. To access
the live webcast, or the subsequent archived recording, visit the
Investors section of the Nektar website at www.nektar.com. The
webcast will be available for replay on Nektar's website for two
weeks following the call.
About NKTR-181
NKTR-181 is the first long-acting,
selective mu-opioid agonist designed to provide potent pain relief
without the inherent high levels of euphoria which lead to abuse
and addiction with standard opioids. The novel molecular
structure of NKTR-181 is designed to have low permeability across
the blood-brain barrier in order to slow its rate of entry into the
brain and attenuate the dopamine release that underlies
euphoria. NKTR-181 is the first opioid molecule to exhibit
reduction in specific CNS-mediated side effects, like euphoria,
through the strategic alteration of brain-entry
kinetics. NKTR-181 is an investigational product and has
not been approved by the FDA or any other regulatory agencies.
Current strategies of abuse deterrence to address the addictive
qualities of standard opioids rely on formulations alone. All
abuse-deterrent formulations are limited in that once the opioid
within the formulation is liberated through tampering, it can
rapidly enter the brain and is highly euphorigenic.
Preclinical data show that the inherent properties of NKTR-181
reduce its rate of entry into the brain compared to standard mu
opioids, regardless of route of administration.12
About the SUMMIT-07 Study Design
SUMMIT-07 used an
enriched-enrollment, randomized withdrawal (EERW) design and
enrolled opioid-naïve patients ages 18 to 75 years who had moderate
to severe non-neuropathic chronic low back pain for at least six
months. The study included an open-label, dose-titration period
followed by a randomized, double-blind, placebo-controlled 12-week
treatment period.
During the open-label titration phase, study participants with
pain scores of between 5 and 9 were titrated on NKTR-181 tablets
administered orally twice daily until they experienced an adequate
and sustained pain response (a drop of at least 2 points and a pain
score below 4 on the numeric rating scale (NRS) of 0-10).
Patients who achieved this were then randomized on a 1:1 basis
to either continue receiving their analgesic dose of NKTR-181 or to
receive placebo (i.e. the active drug was withdrawn) during the
double-blind 12-week treatment period. A total of 610 patients were
randomized into the double-blind treatment period. The
primary outcome was based on assessing worsening of pain in the
placebo arm relative to the active arm for patients who achieved
substantial analgesic responses with NKTR-181. The primary
efficacy endpoint was a change in pain as measured by the change in
a patient's weekly pain score from baseline to week 12 of the
randomized, double-blind, treatment period.
About Opioids and Abuse
Pain is one of the most common
reasons people seek medical treatment.2 A study
published in the American Pain Society's The Journal of Pain
in October 2014 estimated that 19
percent of the U.S. population, or 39 million people, suffer from
persistent pain.5
Opioids are considered the most effective therapeutic option for
pain. In 2016, 230 million opioid prescriptions were written in the
U.S.6 However, these painkillers can cause serious
side effects such as respiratory depression and sedation, and they
have the potential for addiction, abuse and
misuse.7 In 2014, nearly 2 million Americans
either abused or were dependent on prescription opioid pain
relievers.8 One in five Americans say they have a
family member who has been addicted to prescription
painkillers.9 In 2015, there were nearly 22,000
deaths involving prescription opioids in the U.S.10
According to a 2011 Institute of Medicine Report, pain is a
significant public health problem that costs society at least
$560 to 635 billion
annually.2 In the U.S., prescription opioid abuse costs
were about $78.5 billion in
2013.11
About Nektar Therapeutics
Nektar Therapeutics is a
research-based biopharmaceutical company whose mission is to
discover and develop innovative medicines to address the unmet
medical needs of patients. Our R&D pipeline of new
investigational medicines includes treatments for cancer,
auto-immune disease and chronic pain. We leverage Nektar's
proprietary and proven chemistry platform in the discovery and
design of our new therapeutic candidates. 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 which can
be identified by words such as: "plan," "expect," "may," "will" and
similar references to future periods. Examples of forward-looking
statements include, among others, statements we make regarding
the potential therapeutic benefit of NKTR-181 for treating
patients with pain, the potential importance of NKTR-181's
development in the area of new pain medicines, the risks of opioid
abuse resulting from new and existing pain medicines, future
development plans for NKTR-181 (including, but not limited to,
future clinical development plans and future regulatory filings
seeking regulatory approval for NKTR-181), the potential timeframe
for commercial availability of NKTR-181, and certain other
statements regarding the prospects and potential of NKTR-181
specifically, and Nektar's business and technology platform
generally. 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) challenges
and uncertainties inherent in pharmaceutical research and
development, including the uncertainty of future clinical and
regulatory success, where the risk of failure remains high and
failure can unexpectedly occur at any stage prior to regulatory
approval due to lack of sufficient efficacy, safety considerations
or other factors; (ii) the regulatory pathway to review and approve
NKTR-181 for use in patients, even with a Fast Track designation by
the FDA, is subject to substantial uncertainty; (iii) regulations
concerning and controlling the access to opioid-based
pharmaceuticals are strict and there is no guarantee which
scheduling category will apply to NKTR-181 if regulatory
approval is achieved; (iv) the partnering process for NKTR-181 is
at a very early stage and there is therefore substantial
uncertainty as to the timing and terms of a potential partnership,
or the success of our partnering efforts; (v) drug manufacturing
challenges which can delay or render unavailable sufficient
supplies of NKTR-181; (vi) changing standards of care and new
regulations (including, but not limited to, standards and
regulations related to health care cost containment) can affect the
use NKTR-181 and commercial success following a regulatory
approval; (vii) Nektar's patent applications for NKTR-181 may not
issue in one or more jurisdictions, patents that have issued may
not be enforceable, or additional intellectual property licenses
from third parties may be required in the future; (viii) the
outcome of any existing or future intellectual property or other
litigation related to Nektar's proprietary product candidates,
including, without limitation, NKTR-181, is unpredictable and could
have a material adverse effect on our business; and (ix) certain
other important risks and uncertainties set forth in Nektar's
Annual Report on Form 10-K for the year ended December 31, 2016 filed with the Securities and
Exchange Commission on March 1, 2017.
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:
For Investors:
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Jodi Sievers of Nektar
Therapeutics
415-482-5593
For Media:
Dan Budwick of Pure
Communications
973-271-6085
dan@purecommunications.com
- Hyman, Steven E., Harvard Review of Psychiatry. 2(1):43-46,
May/June 1994.
- 2011 National Academy of Sciences. Relieving Pain in America: A
Blueprint for Transforming Prevention, Care, Education and
Research, 2010 Decision Resources, and Harstall, C. How prevalent
is chronic pain? Pain Clinical Updates X, 1-4 (2003).
- Arch Intern Med 2009 February 9;
169(3): 251-258.
- World Health Organization: Priority Medicines for Europe and the World Update Report, 2013;
Background Paper 6.24, Low Back Pain.
-
http://americanpainsociety.org/about-us/press-room/persistent-pain-incidence-news-release.
- IMS, 2016.23.
- Melnikova, I, Pain Market, Nature Reviews Drug Discovery,
Volume 9, 589-90 (August 2010).
- Substance Abuse and Mental Health Services Administration,
National Survey on Drug Use and Health, 2014.
- The Washington Post/Kaiser Family Foundation Survey of
Long-Term Prescription Painkiller Users and Their Household
Members:
http://kff.org/other/report/the-washington-post-kaiser-family-foundation-survey-of-long-term-prescription-painkiller-users-and-their-household-members.
- CDC. Wide-ranging online data for epidemiologic research
(WONDER). Atlanta, GA: CDC,
National Center for Health Statistics; 2016. Available at
http://wonder.cdc.gov.
- Med Care. 2016 Oct;54(10):901-6.
- 2010 Society of Neuroscience Annual Meeting (Nov 13-17, #HHH11).
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SOURCE Nektar Therapeutics