By Pat Anson, Editor

A new opioid medication being developed by Nektar Therapeutics for the treatment of moderate to severe chronic pain has significantly less abuse potential than oxycodone -- even at high doses – according to the results of a new clinical study.

The investigational oral drug – known as NKTR-181 -- is the first analgesic opioid designed to reduce side effects such as euphoria, which can lead to abuse and addiction.

In a small study involving 54 recreational drug users, NKTR-181 had significantly less “drug liking” than oxycodone in the first hours of use. The dosage given to the study participants ranged from a maximum therapeutic dose of 400mg of NKTR-181 to a “supratherapeutic” dose that was 3 to 12 times higher than common doses of oxycodone.

"It is clear from our new study results that NKTR-181 is highly differentiated in this respect from oxycodone, which is a choice drug of abuse.  Further, and critically important in the context of this public health emergency, NKTR-181's less rewarding properties and strong analgesia are inherent to its novel molecular structure and independent of any abuse-deterrent formulation,” said Ivan Gergel, MD, Senior Vice President and Chief Medical Officer of Nektar. 

“Many patients do not receive adequate pain relief because they fear taking conventional opioids, including abuse-deterrent formulations, because of their potential for abuse and addiction.  We believe NKTR-181 is a transformational pain medicine that should significantly advance the treatment of chronic pain and could be a fundamental building block in the fight against prescription opioid abuse.”

In March, NKTR-181 received “fast track” designation from the Food and Drug Administration -- a status that allows for an expedited review of the drug – after Nektar reported positive results from a Phase 3 study of over 600 patients with chronic back pain.  Pain scores dropped by an average of 65% in patients taking NKTR-181 twice daily.

The molecular structure of NKTR-181 is designed to have low permeability across the blood-brain barrier, which slows its rate of entry into the brain – thus reducing the “high” or euphoric effect. Many pain sufferers say they do not get high or experience euphoria from opioid medication, but drug makers and regulators are working to develop painkillers with less risk of abuse and addiction.  

"Getting very high, very fast, is a mark of conventional high-risk, abused opioids," said Jack Henningfield, PhD, vice president at Pinney Associates and adjunct professor at The Johns Hopkins University School of Medicine. "NKTR-181 represents a meaningful advance in the treatment of pain as the first opioid analgesic with inherent brain-entry kinetics that avoids this addictive quality of traditional opioids. This prevents the rapid 'rush' that abusers seek during the critical period immediately after dosing. Importantly, these properties of NKTR-181 are inherent to its molecular structure and are not changed through tampering or route of administration." 

Because NKTR-181 produces less euphoria, Nektar believes it should be scheduled as a Class III or Class IV controlled substance, a less restrictive schedule than Class II medications, a category that includes oxycodone, hydrocodone and many other opioids.

Nektar is a research-based biopharmaceutical company that discovers and develops new drugs for which there is a high unmet medical need. It has a pipeline of new investigational drugs to treat cancer, auto-immune disease and chronic pain.