FDA grants fast track designation to opioid analgesic NKTR-181

The FDA granted fast track designation to NKTR-181, the first full mu-opioid agonist molecule, which is intended to provide pain relief without the high levels of euphoria that sometimes lead to abuse and addiction of other opioids, according to a press release from Nektar Therapeutics, the agent’s manufacturer.

Previously published research has also shown the drug delayed the onset of central nervous system effects and has significantly lower abuse potential scores compared with oxycodone in recreational opioid users. NKTR-181 continues a trend by several manufacturers to create pain management agents that contain abuse-deterrent properties.

“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," Howard W. Robin, president and CEO of Nektar Therapeutics, said in the release. "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."

Several recent studies have shown that many currently available treatments for back pain are largely ineffective.

According to the company, SUMMIT-07, the latest study, used an enriched-enrollment randomized withdrawal trial design in 600 patients new to opioid therapy and with moderate to severe chronic low back pain. These patients were titrated to a tolerated, effective dose of NKTR-181 (100-400 mg twice per day), then entered a double blind, placebo-controlled treatment period in which they were randomly assigned 1:1 to continue the tolerated, effective dose of NKTR-181 or matching placebo (ie, active drug was withdrawn) for a period of 12 weeks.

The release stated that SUMMIT-07 met the primary efficacy endpoint in showing improved chronic back pain relief with NKTR-181 compared with placebo (P = .0019). Secondary endpoints of the study such as general overall status and quality of life were reported as “improved” or “very much improved” when compared to placebo. The most commonly reported adverse events for patients assigned NKTR-181 were nausea (10.4%) and constipation (8.7%), the same adverse events as experienced by patients receiving placebo, though at a higher incidence: nausea (6%); constipation (3%).

"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," Martin Hale, MD, clinical investigator and medical director of Gold Coast Research, said in the release. “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."

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The results of a trial published earlier in this month in Pain Medicine also showed the potential of NKTR-181. In this study, each of the 42 patients were randomly chosen to one of five treatment sequences: 100 mg NKTR-181 in solution, 200 mg NKTR-181 in solution, 400 mg NKTR-181 in solution, 40 mg oxycodone in solution or matching placebo solution.

According to the researchers, at all dosing levels, NKTR-181 had lower drug-liking visual analog scale maximal effect than oxycodone (P < .0001). Drug-liking scores for oxycodone increased rapidly within 15 minutes and peaked at approximately 1 hour postdose, whereas drug-liking scores (and most secondary abuse potential measures) for all doses of NKTR-181 were comparable with placebo for at least the first hour. Further, only the 400-mg drug-liking scores were minimally differentiated vs. placebo from 1.5 to 4 hours, but remained lower than oxycodone (P < .003), and the drug delayed the onset of central nervous system effects.

Researchers also reported that the most frequently occurring treatment-emergent adverse event was generalized pruritus after administration of oxycodone (41.5%). Two hundred milligrams of NKTR-181 caused generalized pruritus in 7.3% of patients, and 400 mg of NKTR-181 caused generalized pruritus in 4.9% of patients. Other adverse effects included nausea with oxycodone (29.3% of patients). For those assigned NKTR-181, the 100-mg dose led to nausea in 2.5% of patients, 200-mg dose led to nausea in 2.4% of patients and 400 mg led to nausea in 7.3% of patients. In addition, researchers wrote that vomiting occurred in 2.4% of patients receiving 200 mg and 400 mg NKTR-181 compared with 24.4% of patients after administration of oxycodone.

“Today's reported efficacy and safety results, along with the human abuse potential data published this past week in Pain Medicine, suggest NKTR-181 may be a major advance toward safer opioid therapy for the treatment of moderate to severe chronic pain," Jack Henningfield, PhD, adjunct professor of behavioral biology, department of psychiatry and behavioral sciences, Johns Hopkins University School of Medicine, said in the release. – by Janel Miller

Reference:

http://ir.nektar.com/releasedetail.cfm?ReleaseID=1017974

Webster L, et al. Pain Med. 2017;doi:10.1093/pm/pnw344

Disclosure: Healio Family Medicine was unable to confirm relevant financial disclosures prior to publication.