New preclinical data presented todat demonstrates that NKTR-181 (Nektar Therapeutics), a mu-opioid analgesic with a novel molecular structure, dramatically reduces abuse liability while providing analgesia comparable to oxycodone and morphine. These data were presented during the poster session entitled “Chronic and Cancer Pain” held today at the American Society of Anesthesiologists (ASA 2010) Annual Meeting in San Diego, California.
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 recent report from the Center for Disease Control and Prevention (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 by the user into a rapid-acting abusable form of an opioid. NKTR-181 is currently in IND-enabling studies and Nektar plans to begin Phase-I clinical studies in the first part of 2011.
“New therapeutics to manage chronic pain without the serious risks associated with existing opioids are desperately needed,” said Lynn R. Webster, MD, Medical Director of Lifetree Clinical Research and Pain Clinic and President, Utah Academy of Pain Medicine. “A novel opioid therapy, such as NKTR-181, with low abuse potential and fewer CNS-related side effects than existing opioids provides great promise for pain practitioners looking for safer, more effective pain management.”
NKTR-181 Data Highlights from ASA 2010
In a preclinical in vivo model of pain, NKTR-181 showed comparable analgesic efficacy to both oxycodone and morphine. In self-administration studies in non-human primates that are used to predict abuse liability of compounds, NKTR-181 showed a marked reduction in self-administration of drug as compared to both oxycodone and morphine. Additionally, in a series of in situ brain perfusion studies, NKTR-181 exhibited a significantly reduced rate of entry into the CNS as compared to oxycodone.
These data were presented at Anesthesiology 2010: American Society of Anesthesiologists Annual Meeting during the poster session entitled “Chronic and Cancer Pain” (Fishburn et al., “NKTR-181, a Novel Opioid Analgesic with Slow Entry into the CNS and Markedly Reduced CNS Side Effects” (Abstract A509), October 17, 2010, 9:00 ? 11:00 AM Pacific time, Room Hall B1-Area G.).
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
[5]Morbidity and Mortality Weekly Report (MMWR), Emergency Department Visits Involving Nonmedical Use of Selected Prescription Drugs United States, 2004?2008, 59(23);705-709 (June 2010)
