SUMMIT-07 Study Favorable for New Opioid Candidate

A new kind of opioid that holds promise of being non-addictive cleared a hurdle.

Nektar Therapeutics announced favorable phase 3 results on a first-in-class opioid known as NKTR-181.

The drug is a new chemical entity that the company describes as the first full mu-opioid agonist molecule designed to provide potent pain relief but without euphoric effects.

The product may relieve pain without creating a potential for abuse and addiction, the company said in a news release.

The US Food and Drug Administration (FDA) is reviewing the product under a Fast Track designation for the treatment of moderate to severe chronic pain.

In a study known as SUMMIT07, of NKTR-181, the drug or placebo were given twice daily to over 600 patients with moderate to severe chronic low back pain. All patients were opioid naïve.

The company said 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 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 randomized 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continue to receive the tolerated, effective dose of NKTR-181 or to receive matching placebo (i.e. active drug was withdrawn) for a period of 12 weeks.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 randomization, n=610).

The primary endpoint of the study 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 analysis of primary and key sensitivity showed that:

• During the double-blind randomized treatment period of the trial, average pain scores increased more in the placebo arm versus NKTR-181 at week 12 from randomization baseline (1.46, placebo versus 0.92, NKTR-181, p=0.0019, n=610).
• 83% of patients completed the 12-week double-blind randomized 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).

It met 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 favorable safety profile and was well tolerated. During the double-blind randomized 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.

Patients randomized to NKTR-181 as compared to placebo reported more favorable 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."

The release is here.