Nektar’s opioid analgesic meets endpoints in Phase 3 Study of chronic pain

Nektar Therapeutics announced positive results from the SUMMIT-07 Phase 3 efficacy study of NKTR-181, an opioid analgesic. NKTR-181 is a new chemical entity that is the first full mu-opioid agonist molecule designed to provide potent pain relief without the high levels of euphoria that can lead to abuse and addiction with standard opioids.

The US Food and Drug Administration (FDA) has granted the investigational medicine NKTR-181 fast track designation for the treatment of moderate to severe chronic pain.

"The data from this efficacy study are extremely important because they demonstrate that NKTR-181 produces strong analgesia in patients suffering from chronic pain while NKTR-181 has also demonstrated significantly lower abuse potential than oxycodone in a human abuse potential study," said clinical investigator Martin Hale, MD, medical director of Gold Coast Research.

Opioid addiction

"While standard opioid analgesics, including abuse-deterrent formulations, have been the most effective way to treat chronic pain, they are associated with serious safety concerns and many opioid-naïve patients fear taking them because of the potential for abuse and addiction. The data for NKTR-181 suggest that it is a transformational pain medicine that could fundamentally change how we treat patients with chronic pain conditions."

Study specifics

The SUMMIT-07 study compared twice-daily dosing of NKTR-181 tablets to placebo in the treatment of over 600 patients with moderate to severe chronic low back pain who were new to opioid therapy (opioid-naïve). The clinical trial met the primary efficacy endpoint of the study in demonstrating significantly improved chronic back pain relief with NKTR-181 compared to placebo (p=0.0019). Key secondary endpoints of the study were also met with high statistical significance.

The Phase 3 SUMMIT-07 study used an enriched-enrolment randomised withdrawal (EERW) trial design in patients with moderate to severe chronic low back pain. The trial included an open-label titration period in which patients were titrated to a tolerated, effective dose of NKTR-181 (100 mg to 400 mg twice-daily).

Following this open-label titration period, patients entered a double-blind, placebo-controlled treatment period in which they were randomised 1:1 to either continue to receive the tolerated, effective dose of NKTR-181 or to receive matching placebo (i.e. active drug was withdrawn) for a period of 12 weeks.

During the open-label titration period of the trial in which patients were titrated to a tolerated, effective dose of NKTR-181, average pain scores dropped by 65% (from 6.73 at screening to 2.32 at randomisation, n=610).

Endpoints of trial

The primary endpoint of the study was mean change in the weekly average pain score in the double-blind randomised treatment period from baseline (end of open-label titration period) to week 12 (end of double-blind randomised treatment period).

Primary and key sensitivity analyses:

• During the double-blind randomised treatment period of the trial, average pain scores increased more in the placebo arm versus NKTR-181 at week 12 from randomisation baseline (1.46, placebo versus 0.92, NKTR-181, p=0.0019, n=610).
• 83% of patients completed the 12-week double-blind randomised treatment period and for these study completers, average pain scores increased more in the placebo arm versus NKTR-181 at week 12 from baseline (1.25, placebo versus 0.56, NKTR-181, p<0.0001, n=504).

Key secondary endpoints:

• A statistically significant proportion of patients on NKTR-181 experienced pain reductions greater than 30% compared to placebo (71.2% versus 57.1%; p=0.0003).
• A statistically significant proportion of patients on NKTR-181 experienced pain reductions greater than 50% compared to placebo (51.1% versus 37.9%; p=0.001).
• A statistically significant proportion of patients on NKTR-181 reported their general overall status and quality of life as "improved" or "very much improved" compared to placebo as assessed by the Patient’s Global Impression of Change (PGIC) of pain medication questionnaire (51.5% versus 33.2%; p<0.0001).

The study also demonstrated that NKTR-181 had a favourable safety profile and was well tolerated. During the double-blind randomised treatment period, the most commonly reported adverse events for patients (>5%) were nausea (10.4%) and constipation (8.7%) in the NKTR-181 arm as compared to nausea (6.0%) and constipation (3.0%) in the placebo arm.

Sleep outcomes

Patients randomised to NKTR-181 as compared to placebo reported more favourable sleep outcomes as measured by the validated Medical Outcomes Study (MOS) Sleep Scale, which captures debilitating aspects of sleep most strongly associated with chronic pain. Patients reported better overall quality of sleep with less sleep problems on NKTR-181 versus placebo. There were no differences in daytime sleepiness on NKTR-181 versus placebo.

Full data from the SUMMIT-07 study will be presented at a medical meeting in the second half of 2017.

"As a new molecule, NKTR-181 has a highly differentiated profile with the potential to be one of the most important advancements in pain medicine," said Howard W. Robin, President and CEO of Nektar Therapeutics. "Given the seriousness of the current opioid epidemic in the U.S. and the significant number of people battling chronic pain, we are committed to bringing this new molecule to patients and physicians as quickly as possible."