SAN FRANCISCO, Feb. 27, 2012 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced a presentation of positive clinical data for NKTR-181, its new oral opioid analgesic molecule, at the 2012 American Academy of Pain Medicine's 28th Annual Meeting (AAPM). NKTR-181 is a novel mu-opioid agonist molecule, which was designed to have a slow rate of entry into the brain to reduce the attractiveness of the molecule as a target of abuse and to reduce its CNS-mediated side effects. NKTR-181 was created using Nektar's proprietary polymer conjugate technology and its differentiating properties are inherent to the design of the new molecule. As a new molecular structure, NKTR-181 is unique in that it does not rely on a formulation approach to prevent its conversion into a more abusable form of an opioid.
Clinical results were presented at AAPM from a human Phase 1 study which evaluated the pharmacokinetics, pharmacodynamics, and safety of oral doses of NKTR-181 as compared to placebo over an 8-day treatment period in healthy subjects. Using pupil constriction as a measure of the onset of central opioid effect, the study showed that NKTR-181 enters the brain slowly and produces centrally-mediated opioid effects that are dose-dependent and statistically meaningful (P<0.001) following twice daily oral doses of 200-400 mg. Further, NKTR-181 enters the CNS from the plasma at a rate approximately ten-times slower than historical published rates for oxycodone.(1) NKTR-181's slow rate of entry into the CNS may reduce the euphoria and other CNS side effects that are associated with rapid CNS uptake of current standard opioid therapies.
"NKTR-181 is an exciting new approach to opioid analgesia," said Lynn R. Webster, MD, Medical Director of Lifetree Clinical Research. "The human data now show us that NKTR-181 crosses into the brain slowly across a wide range of doses, over multiple days of dosing, and also achieves a sustained analgesic response. By slowing the rate of entry into the brain, NKTR-181 is designed to have less euphoria, sedation and respiratory depression than traditional opioid compounds. Individuals with a higher risk of abusing opioids prefer rapid onset of euphoria, which means NKTR-181 should be less attractive as a drug of abuse. NKTR-181 represents an exciting developmental advance in pain. This new human data support its further clinical development as a compelling therapeutic for the treatment of chronic pain."Data presented at AAPM show the positive analgesic properties of NKTR-181 in humans. NKTR-181 produced dose-dependent analgesic responses in two separate models of pain used to measure central and peripheral analgesic activity in healthy subjects. In a cold-pressor test pain model measuring latency-to-hand-removal (LHR), the 200 mg dose of NKTR-181 given twice-daily over the 8-day dosing period demonstrated the extent and duration of analgesic effect of NKTR-181 administration. Results show a significant analgesic effect as compared to placebo (P<0.01, n=12) over the entire dosing period. In addition, a model of induced UVB injury was also used to demonstrate the extent and duration of analgesic effect produced by NKTR-181. Results show that NKTR-181 has both centrally-mediated and peripherally-mediated analgesic effects. In this model, data was presented on NKTR-181 at doses of 300 mg and 400 mg demonstrating its significant analgesic and anti-hyperalgesic effect (measured as change from baseline) following mechanical and thermal stimulation, with p-values of P<0.009 and P<0.03, respectively (n=12).