First-in-Class Opioid Analgesic Evaluated for Chronic Back Pain
The primary efficacy endpoint was mean change in weekly average pain score in the treatment period from baseline
Nektar Therapeutics announced positive results from the SUMMIT-07 Phase 3 study of NKTR-181, a first-in-class opioid analgesic for the treatment of moderate to severe chronic pain.
SUMMIT-07 is designed as an enriched-enrollment, randomized withdrawal (EERW) trial in opioid-naïve patients aged 18-75 years who had moderate to severe non-neuropathic chronic low back pain for at least 6 months. The study included an open-label dose-titration period in which patients were titrated to a tolerated, effective dose of NKTR-181 (100mg to 400mg twice daily). The titration period was followed by a randomized, double-blind, placebo-controlled treatment phase where patients received either the established NKTR-181 dose or matching placebo for a period of 12 weeks. The primary efficacy endpoint was mean change in the weekly average pain score in the double-blind randomized treatment period from baseline (end of open-label titration period) to Week 12 (end of double-blind randomized treatment period).
The study met its primary endpoint, showing that treatment with NKTR-181 demonstrated significantly improved chronic back pain relief compared to placebo (P=0.0019). During the open-label titration phase, patients receiving a tolerated, effective dose of NKTR-181 had average pain scores dropped by 65%, from a score of 6.73 at screening to 2.32 at randomization. During the double-blind treatment phase, average pain scores increased more in the placebo arm compared to the NKTR-181 arm at Week 12 (1.46 vs. 0.92 respectively, P=0.0019). For the 83% of patients who completed the 12-week treatment period, average pain scores increased more in patients treated with placebo vs. those with NKTR-181 (1.25 vs. 0.56 respectively, P<0.0001).
The study also met its key secondary endpoints, showing that a statistically significant proportion of patients treated with NKTR-181 experienced pain reductions greater than 30% (P=0.0003) and 50% (P=0.001), and reported their general overall status and quality of life as "improved" or "very much improved," as assessed by the Patient's Global Impression of Change (PGIC) of pain medication questionnaire (P<0.0001), compared to placebo.
The study found NKTR-181 to have a favorable and tolerable safety profile, with the most common adverse events presenting as nausea and constipation. In addition, patients treated with NKTR-181 reported more favorable sleep outcomes, as measured by the validated Medical Outcomes Study (MOS) Sleep Scale, including better overall quality of sleep with less sleep problems. No differences in daytime sleepiness between NKTR-181 and placebo were reported. Complete detailed results of the SUMMIT-07 study will be presented at a medical meeting in the second half of 2017.
NKTR-181 is a first-in-class, long-acting, selective mu-opioid agonist. Its novel molecular structure is designed to have low permeability across the blood-brain barrier, thereby slowing rate of entry into the brain and attenuating dopamine release, without compromising its potent pain relief. The end result is a reduction in CNS-mediated side-effects, such as euphoria, the cause of abuse and addiction with standard opioids.
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