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