A phase 3 trial of Nektar Therapeutics’ chronic pain asset NKTR-181 has met its primary endpoint. The clinical trial linked the mu-opioid to a statistically significant improvement in pain scores over placebo, giving Nektar efficacy data to back up an earlier study on the candidate’s abuse potential.
Nektar enrolled opioid-naive patients with moderate to severe chronic low back pain in the trial. All the subjects were titrated up to a tolerable, effective dose of NKTR-181—up to 400 mg twice a day—before being randomized to either continue on the experimental drug or switch to placebo. This marked the start of the 12-week double-blind randomized treatment period. The primary endpoint looked at changes in pain scores over this period.
During the titration period, pain scores fell from 6.73 to 2.32, a 65% decline. Then, once subjects were randomized, the pain scores of the treatment and placebo cohorts rose respectively by 0.92 and 1.46. That difference was enough for the trial to hit its primary endpoint with a p-value of 0.0019. The difference was more pronounced among the 83% of patients who completed the trial. In this subgroup, the placebo and treatment pain scores rose by 1.25 and 0.56, respectively.
“The data from this efficacy study are extremely important because they demonstrate that NKTR- 181 produces strong analgesia in patients suffering from chronic pain,” clinical investigator Martin Hale, M.D., medical director of Gold Coast Research, said in a statement.
Nektar also reported the performance of NKTR-181 against some secondary endpoints. The trial found statistically significant differences in the proportion of patients in the treatment and placebo groups who achieved 30% and 50% reductions in pain. In the NKTR-181 arm, 71.2% of patients hit the 30% mark and 51.1% of subjects achieved a decline of 50% or more.
Safety data show 10.4% of patients in the treatment arm experienced nausea and 8.7% suffered from constipation. Neither adverse event affected more than 5% of patients in the placebo group. The data come from the double-blind randomized treatment period. Nektar is yet to post safety data on the titration period.
In a mid-stage trial of the drug that reported data in 2013, 53 subjects stopped treatment during the titration period because of adverse events. The top-line data for the phase 3 lack that detail, as well as information on the dropout rate in each arm during the study period.
Nausea and constipation are side effects common to the broader class of opioids, the market for which Nektar is seeking to upend. Its proposition for NKTR-181 is built on the idea it can provide effective pain relief without raising the risk of addiction and abuse. These latter characteristics were looked at in an earlier study, in which NKTR-181 achieved “drug liking” and “feeling high” scores comparable to placebo.
Nektar thinks the chemical structure of NKTR-181 underpins these findings. The molecule is designed to enter the brain at a slower rate than conventional opioids. As such, Nektar thinks it will cause less euphoria than existing drugs and, in doing so, be less likely to be abused.