NKTR-181
| NKTR-181 |
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Analgesia for management of moderate to severe pain |
Phase 1 |
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NKTR-181 is a mu-opioid analgesic investigational drug candidate with a novel molecular structure designed to provide potent pain relief while reducing the serious side effects of respiratory depression, sedation and abuse potential associated with conventional opioids.
Market Overview
Pain is the most common symptom for which patients seek medical attention.1 According to the American Pain Society, the prevalence of chronic pain in the United States is estimated to be 35.5% or 105 million people. Chronic pain costs more than $100 billion per year in direct health-care expenditures and lost work time. Opioids are considered to be the most effective therapeutic option for pain and have over $10 billion a year in sales in the U.S. alone.2,3 However, opioids cause significant problems for physicians and patients because of their serious side effects such as respiratory depression and sedation, as well as the risks they pose for addiction, abuse, misuse, and diversion. The U.S. Food and Drug Administration has cited prescription opioid analgesics as being at the center of a major public health crisis of addiction, misuse, abuse, overdose and death.4 A 2010 report from the Centers for Disease Control (CDC) notes that emergency room visits tied to the abuse of prescription painkillers is at an all-time high, having increased 111 percent over a five-year period.5
NKTR-181 was uniquely designed to cross the blood-brain barrier at a substantially slower rate than other opioid therapies. With a reduced rate of entry into the CNS, NKTR-181 has the potential to eliminate not only the euphoria that underlies opioid abuse liability and dependence but also the serious CNS-related side effects of respiratory depression and sedation. The unique molecular design of the polymer drug conjugate also prevents conversion of NKTR-181 into a rapid-acting abusable form of an opioid. As a result, NKTR-181 has the potential to be a highly effective analgesic with a highly favorable safety profile and reduced abuse potential.
NKTR-181 has completed Phase 1 clinical development to assess its pharmacokinetics, pharmacology, safety and efficacy. In the Phase 1 multiple ascending dose study, NKTR-181 produced a dose-dependent and sustained analgesic response in a model of pain used in healthy subjects to measure central analgesic activity. NKTR-181 exhibited predictable dose-linear pharmacokinetics across all dose levels with an average half-life of approximately 12 hours and no evidence of pharmacological tolerance over the 8 days of twice-daily dosing. The sustained central response, analgesic effect and safety profile over a 12-hour period supports a twice-daily (BID) dosing schedule.
Full results and data from this multiple ascending dose Phase 1 study of NKTR-181 have been accepted for presentation at the 2012 American Academy of Pain Medicine's 28th Annual Meeting to be held February 23 — 26, 2012.
The multiple ascending dose study is the second study in the Phase 1 clinical program for NKTR-181. Positive results from the first Phase 1 study, which was a single ascending dose trial in 110 healthy subjects, were presented at the American Academy of Pain Management (AAPM) Annual Meeting in September 2011.
NKTR-181 is currently being prepared for Phase 2 development in chronic pain patients in mid-2012.
| May 17-19, 2012 |
American Pain Society 31st Annual Scientific Meeting |
Honolulu, HI |
| February 24, 2012 |
American Academy of Pain Medicine Annual Meeting |
Palm Springs, CA |
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SESSION: Poster Group 2
DATE: February 24, 2012
TIME: 5:45 PM
LOCATION: Oasis 1/2 Exhibit Hall of the Palm Springs Convention Center
TITLE: "Multiple Dose Pharmacokinetics and Pharmacodynamics of the New Oral Opioid Analgesic NKTR-181"
AUTHOR: Lynn Webster, M.D., et al.
POSTER NUMBER: 282B
TITLE: " NKTR-181: A Novel, Orally Available Mu-Opioid Agonist with Reduced Rate and Extent of CNS Exposure Exhibits Comparable Analgesic Efficacy but Reduced Abuse and CNS Side Effect Compared to Oxycodone"
AUTHOR: Kathleen Gogas, Ph.D., et al.
POSTER NUMBER: 258
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References:
1 Harstall, C. How prevalent is chronic pain? Pain Clinical Updates X, 1-4 (2003).
2 IMS, NSP, NPA and Defined Health 2010 Estimates.
3 Melnikova, I, Pain Market, Nature Reviews Drug Discovery, Volume 9, 589-90 (August 2010).
4 Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, "Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioid Analgesics" July 23-4, 2010.
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