Indication: Treatment of moderate to severe chronic low back pain
Discovered and Wholly Owned by Nektar
NKTR-181, a first-in-class opioid analgesic, 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
About Opioids and Pain Management
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 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
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 and sedation, through the strategic alteration of brain-entry kinetics.
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
The U.S. Food and Drug Administration (FDA) has granted NKTR-181 Fast Track designation for the treatment of moderate to severe chronic pain. NKTR-181 is an investigational product and has not been approved by the FDA or any other regulatory agencies.
SUMMIT-07 Phase 3 Study
The SUMMIT-07 Phase 3 study is an enriched-enrollment, randomized withdrawal (EERW) efficacy and safety study evaluating NKTR-181 versus placebo in opioid-naïve patients with chronic low back pain. The SUMMIT Phase 3 program also includes a 52-week long term safety study (SUMMIT-LTS) which is ongoing and a second human abuse potential (HAP) study which is currently underway. Information about the SUMMIT studies can be found on clinicaltrials.gov.
1Hyman, Steven E., Harvard Review of Psychiatry. 2(1):43-46, May/June 1994.
22011 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).
3Arch Intern Med 2009 February 9; 169(3): 251-258.
4World Health Organization: Priority Medicines for Europe and the World Update Report, 2013; Background Paper 6.24, Low Back Pain.
7Melnikova, I, Pain Market, Nature Reviews Drug Discovery, Volume 9, 589-90 (August 2010).
8Substance Abuse and Mental Health Services Administration, National Survey on Drug Use and Health, 2014.
9The 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.
10CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2016. Available at http://wonder.cdc.gov.
11Med Care. 2016 Oct;54(10):901-6.
- Clinical Pain Advisor: Mu-Opioid Analgesic in Phase III Offers Hope for the Management of Chronic Pain Without Addictive Side Effects
- MIT Technology Review: Opioids without Addiction
- Medscape Medical News: Novel Opioid May Deter Abuse Through Slow-Acting Analgesia
- BioCentury: BioCentury: BioCentury features Phase 1 NKTR-181 data in the Bernstein Report on BioBusiness
Pain Medicine - March 2017
- Original Research Article: Human Abuse Potential of the New Opioid Analgesic Molecule NKTR-181 Compared with Oxycodone
IASP 26th Annual World Congress on Pain
- Poster L00055: NKTR-181, a novel mu opioid analgesic with inherently low abuse potential and efficacy in multiple preclinical models of pain
2016 American Academy of Pain Management Annual Meeting
2013 College on Problems of Drug Dependence (CPDD) Annual Meeting
- Poster: Abuse Potential Assessment of Novel Opioid Analgesic NKTR-181: Implications for Labeling and Scheduling
2012 American Association of Pharmaceutical Scientists Annual Meeting
2012 American College of Clinical Pharmacology Annual Meeting
- Poster: New Oral Opioid Analgesic NKTR-181: Bioequivalence between Tablet and Aqueous Solution and Lack of Food Effect
- Poster: Mixed-Effects PK/PD Analysis of NKTR-181, a New Oral Opioid Analgesic in Healthy Subjects
2012 American Academy of Pain Medicine 28th Annual Meeting
- Poster: NKTR-181: An Orally Available Mu-Opioid Agonist with Slow Rate of Uptake into the CNS, Exhibits Comparable Analgesic Efficacy with Reduced Abuse Liability and CNS Mediated Side Effects Compared to Oxycodone
- Poster: Multiple Dose Pharmacokinetics and Pharmacodynamics of the New Oral Opioid Analgesic NKTR-181
2011 American Academy of Pain Management 22nd Annual Meeting
- Poster: Pharmacokinetics and Pharmacodynamics of Oral NKTR-181, a Novel Opioid Analgesic: Results of a Single Ascending Dose Phase 1 Study
- Poster: NKTR-181: A Novel Opioid Analgesic That Exhibits Reduced Abuse Potential and Maintains Full Analgesic Activity Following Repeat Dosing in Preclinical Rodent Models
2011 Society for Toxicology 50th Annual Meeting & ToxExpo
- Poster: NKTR-181, a Novel Polymer Conjugated Opioid Agonist, Demonstrates Reduced Toxicity and CNS Side Effects Relative to Oxycodone
2010 Society for Neuroscience 40th Annual Meeting
- Poster: NKTR-181: A novel opioid analgesic with slowed CNS entry shows reduced abuse liability and CNS side effects
- Poster: Controlling the rate of entry to the CNS by polymer conjugation
American Society of Anesthesiologists (ASA) Annual Meeting - Anesthesiology 2010
- Abstract #A509: NKTR-181, a Novel Opioid Analgesic with Slow Entry into CNS and Markedly Reduced CNS Side Effects
5th Annual Frontiers of Clinical Investigation Symposium - Pain 2010: From Bench to Bedside
- March 20, 2017: NKTR-181 Meets Primary and Secondary Endpoints in Phase 3 SUMMIT-07 Study in Chronic Pain
- February 25, 2015: Nektar Announces Start of Phase 3 SUMMIT-07 Study of NKTR-181 in Patients with Chronic Low Back Pain
- September 26, 2013: Nektar Announces Preliminary Topline Results from Phase 2 Efficacy Study for NKTR-181 in Chronic Pain Patients with Osteoarthritis of the Knee
- June 19, 2013: Nektar Therapeutics Presents Positive Data from Human Abuse Liability Study for NKTR-181, a First-in-Class Investigational Opioid to Treat Chronic Pain, at 2013 Annual Meeting of The College on Problems of Drug Dependence
- July 24, 2012: Nektar Announces Start of Enrollment in Phase 2 Study of NKTR-181, a Novel Opioid Analgesic Molecule, for Treatment of Chronic Pain
- February 27, 2012: Nektar Presents Positive Proof-of-Concept Clinical Data for Its New Opioid Molecule, NKTR-181, at American Academy of Pain Medicine's 28th Annual Meeting
- December 13, 2011: Nektar Announces Positive Clinical Data from Second Phase 1 Clinical Study of NKTR-181, a Novel Opioid Analgesic Molecule to Treat Chronic Pain