Indication: Treatment of moderate to severe chronic low back pain
Discovered and Wholly Owned by Nektar
NKTR-181 is a first-in-class, mu-opioid analgesic investigational drug candidate with a novel molecular structure designed to provide potent pain relief with a slow rate of entry into the brain. This slow rate of entry is designed to reduce the euphoria that can lead to the abuse of current opioid analgesics.1
About Opioids and Pain Management
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.3
Opioids are considered the most effective therapeutic option for pain but can cause serious side effects such as respiratory depression and sedation and have the potential for addiction, abuse and misuse.4,5 In 2014, nearly two million Americans either abused or were dependent on prescription opioid pain relievers.6 According to a 2011 Institute of Medicine Report, pain is a significant public health problem that costs society at least $560-$635 billion annually. This includes the total incremental cost of health care due to pain from ranging between $261 to $300 billion and $297-$336 billion due to lost productivity (based on days of work missed, hours of work lost, and lower wages).7
NKTR-181 is a new chemical entity (NCE) that Nektar Therapeutics created using its proprietary small molecule polymer conjugate technology. NKTR-181 has several potential differentiating properties which are designed as part of the structure of the molecule, including a slow rate of entry into the central nervous system (CNS) as measured by pupillometry (contraction of the pupils) and a pharmacokinetic profile that will allow it to be administered to chronic pain patients twice-a-day to allow for around the clock pain control. NKTR-181 is not a reformulation of an approved opioid, which is a commonly-used method to attempt to prevent the manipulation of existing long-acting opioid drugs into more abusable forms. The U.S. Food and Drug Administration (FDA) has granted NKTR-181 Fast Track designation for the treatment of moderate to severe chronic pain.
SUMMIT Phase 3 Program
The SUMMIT Phase 3 program for NKTR-181 includes two efficacy and safety studies and a 52-week long-term safety study (SUMMIT-LTS). Enrollment is complete in the first Phase 3 efficacy study (SUMMIT-07) which will evaluate NKTR-181 versus placebo in opioid-naïve patients with chronic low back pain. The SUMMIT Phase 3 program will also include a Phase 3 efficacy and safety trial in people who are opioid-experienced (SUMMIT-12). 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).
4IMS, NSP, NPA and Defined Health 2013 Estimates.
5Melnikova, I, Pain Market, Nature Reviews Drug Discovery, Volume 9, 589-90 (August 2010).
6Substance Abuse and Mental Health Services Administration, National Survey on Drug Use and Health, 2014.
- 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
- Poster L00055: NKTR-181, a novel mu opioid analgesic with inherently low abuse potential and efficacy in multiple preclinical models of pain
- Poster: NKTR-181 efficacy in multiple preclinical models of pain
- Poster: 2013 College on Problems of Drug Dependence (CPDD) Annual Meeting - June 2013 - Abuse Potential Assessment of Novel Opioid Analgesic NKTR-181: Implications for Labeling and Scheduling
- Poster: American Association of Pharmaceutical Scientists Annual Meeting — October 2012 — Interspecies Comparison of Pharmacokinetics of the Novel Opioid Analgesic NKTR-181s
- Poster: American College of Clinical Pharmacology Annual Meeting — September 2012 — New Oral Opioid Analgesic NKTR-181: Bioequivalence between Tablet and Aqueous Solution and Lack of Food Effect
- Poster: American College of Clinical Pharmacology Annual Meeting — September 2012 — Mixed-Effects PK/PD Analysis of NKTR-181, a New Oral Opioid Analgesic in Healthy Subjects
- Poster: American Academy of Pain Medicine 28th Annual Meeting: Pain Medicine — February 2012 —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: American Academy of Pain Medicine 28th Annual Meeting: Pain Medicine — February 2012 — Multiple Dose Pharmacokinetics and Pharmacodynamics of the New Oral Opioid Analgesic NKTR-181
- Poster: American Academy of Pain Management 22nd Annual Meeting — September 2011 — Pharmacokinetics and Pharmacodynamics of Oral NKTR-181, a Novel Opioid Analgesic: Results of a Single Ascending Dose Phase 1 Study
- Poster: American Academy of Pain Management 22nd Annual Meeting — September 2011 — NKTR-181: A Novel Opioid Analgesic That Exhibits Reduced Abuse Potential and Maintains Full Analgesic Activity Following Repeat Dosing in Preclinical Rodent Models
- Poster: Society for Toxicology 50th Annual Meeting & ToxExpo — March 2011 — NKTR-181, a Novel Polymer Conjugated Opioid Agonist, Demonstrates Reduced Toxicity and CNS Side Effects Relative to Oxycodone
- Poster: Society for Neuroscience 40th Annual Meeting — November 2010 — NKTR-181: A novel opioid analgesic with slowed CNS entry shows reduced abuse liability and CNS side effects"
- Poster: Society for Neuroscience 40th Annual Meeting — November 2010 — "Controlling the rate of entry to the CNS by polymer conjugation"
- Abstract #A509: American Society of Anesthesiologists (ASA) Annual Meeting - Anesthesiology 2010 — October 2010 — "NKTR-181, a Novel Opioid Analgesic with Slow Entry into CNS and Markedly Reduced CNS Side Effects"
- Poster: 5th Annual Frontiers of Clinical Investigation Symposium - Pain 2010: From Bench to Bedside — October 2010 — "NKTR-181: A Novel Opioid With Slowed Brain Entry Shows Low Abuse Liability and Reduced CNS Side Effects"
- 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