"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
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
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continue to receive the tolerated, effective dose of NKTR-181 or to receive matching placebo (i.e. active drug was withdrawn) for a period of 12 weeks.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
"It is clear that there is a pressing societal need for better and safer analgesics," said Dr.
Conference Call and Webcast Information
Nektar will host a conference call and webcast presentation today,
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
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
Opioids are considered the most effective therapeutic option for pain. In 2016, 230 million opioid prescriptions were written in the
According to a 2011
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
- Hyman, Steven E., Harvard Review of Psychiatry. 2(1):43-46, May/
National Academy of Sciences. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research, 2010 Decision Resources, and Harstall, C. Howprevalent 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 Europeand the World Update Report, 2013; Background Paper 6.24, Low Back Pain.
- 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 Surveyof 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.
Society of NeuroscienceAnnual Meeting ( Nov 13-17, #HHH11).
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