‘Opioid of the Future’ Postponed

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is tapping the brakes on NKTR-181, an experimental opioid pain medication that has less abuse potential than traditional opioids like oxycodone or hydrocodone.

In an SEC filing, Nektar Therapeutics said it received a letter from the FDA on July 23 saying the agency was postponing all advisory committee meetings for opioid analgesics, including one scheduled for August 21 to discus Nektar’s new drug application for NKTR-181.

The FDA was due to make a final decision on NKTR-181 eight days later, but that too is apparently being postponed while the agency considers “a number of scientific and policy issues relating to this class of drugs.”

Nektar called NKTR-181 the “opioid of the future” because it is the first full mu-opioid agonist that can provide pain relief without the euphoria or “high” that can lead to abuse and addiction.

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.

In a Phase III clinical study, patients with chronic back pain reported that their pain scores dropped an average of 65% when taking NKTR-181 twice daily. Safety studies also found that recreational drug users had significantly less “drug liking” of NKTR-181 when compared to oxycodone.

NEKTAR IMAGE

NEKTAR IMAGE

The research was so promising the FDA gave NKTR-181 “fast track” designation to speed its development. Nektar executives told PNN two years ago they were hopeful the drug would be approved in late 2018, with a commercial launch early this year.

Obviously that didn’t happen. And the FDA’s fast track has turned into a slow walk.

Two FDA advisory committees met last month and decided “much better-quality data” was needed before approving any new opioids — even ones with low risk of abuse.  

The agency has been under growing public and political pressure to tighten its regulation of opioids. In February, a 60 Minutes report claimed the FDA “opened the floodgates” to the opioid epidemic by approving the use of OxyContin for chronic pain. The following month, the agency received a petition from Public Citizen calling for a moratorium on new opioid approvals because the agency “can no longer be trusted” due to its “poor record” of regulating opioids.

On July 25, Howard Robin, Nektar’s President and CEO, sold 100,000 shares of Nektar for $3.1 million. A spokesman said the sale was previously scheduled due to expiring options. The company’s chief financial officer and a director also sold shares this month. Nektar shares (NASDAQ: NKTR) lost about 10% of their value after the SEC filing was made public.

New Opioid Painkiller Has Less Abuse Potential

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.”

nektar therapeutics

nektar therapeutics

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.

New Opioid Relieves Pain Without the ‘High’

By Pat Anson, Editor

Nektar Therapeutics has announced positive results from Phase III study showing that a new opioid medication significantly reduces pain without the high levels of euphoria that can lead to abuse and addiction.

The company also said the Food and Drug Administration has given the medication – known as NKTR-181 – “fast track” designation for the treatment of moderate to severe chronic pain, a status that allows for an expedited review of the drug.

Many pain sufferers say they do not get "high" or experience euphoria from opioid pain medication. But drug makers and government regulators are seeking to develop painkillers with less risk of abuse and addiction.  

"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.

"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."

The placebo controlled study involved 610 patients with moderate to severe chronic low back pain who had not taken opioids before. During the open-label phase of the study, pain scores dropped by an average of 65% in patients taking NKTR-181 twice daily.

The company said over half the patients (51.5%) on NKTR-181 reported their general overall status and quality of life "improved" or "very much improved" compared to patients taking a placebo. 

They also reported better overall quality of sleep, with less sleep disturbance and fewer sleep problems. There were no differences in daytime sleepiness on NKTR-181 versus placebo. The drug was generally well-tolerated, although some patients reported nausea, constipation and somnolence.

Nektar is currently conducting another Phase III study to evaluate the safety and tolerability of NKTR-181 in 638 patients with chronic low back pain or chronic non-cancer pain.

The company says NKTR-181 is the first opioid molecule to provide pain relief without high levels of euphoria and sedation. The molecular structure of NKTR-181 is designed to have low permeability across the blood-brain barrier in order to slow its rate of entry into the brain.

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.