Nektar Therapeutics announced submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for NKTR-181, a new molecular entity (NME) and the first analgesic opioid molecule to exhibit a reduced incidence of specific CNS-mediated side effects, such as euphoria, through the targeted alteration of brain-entry kinetics.
"The submission of the NDA for NKTR-181 is an important milestone for Nektar, and we would like to thank our employees, investigators, clinical trial sites and most importantly the patients and families of those living with chronic pain for all of their help in the development of this medicine," said Steve Doberstein, Ph.D., Senior Vice President of Research and Development and Chief Development Officer at Nektar Therapeutics. "This innovative investigational medicine separates analgesic efficacy from the high levels of euphoria that too often lead to the abuse and addiction of traditional opioids."
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The NDA is supported by a clinical and nonclinical data package. The clinical data submitted in the NDA comprised 15 studies in 2,234 subjects and includes: a 600-patient efficacy study in patients with chronic low back pain who are new to opioid therapy; a 630-patient long-term 52-week safety study in patients with noncancer pain, who are new to opioid therapy, as well as those who are experienced with opioid therapy; pharmacokinetic/pharmacodynamic studies in over 450 subjects; and two human abuse potential studies evaluating both therapeutic and supratherapeutic doses of NKTR-181 versus an oxycodone control in recreational drug users.
Low back pain is the second most common cause of disability for adults in the U.S. Approximately 149 million work days are lost every year because of low back pain, with total costs estimated to be $100 to 200 billion a year (of which two-thirds is due to lost wages and lower productivity).
NKTR-181 is the first long-acting, selective full mu-opioid agonist designed to provide potent pain relief, without the inherent high levels of euphoria, which lead to abuse and addiction with standard opioids. The novel 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 and attenuate the dopamine release that underlies euphoria. In addition, NKTR-181 has a 14-hour elimination half-life to enable twice-daily dosing for pain control.
Current and past strategies of abuse deterrence to address the addictive properties of standard opioids rely on formulations alone. However, all abuse-deterrent formulations are pre-cursors to highly euphorigenic rapid-acting opioids, which can be liberated through tampering.
NKTR-181 is not a prodrug, a reformulation, or a drug product formulated for sustained release of an existing opioid. Nonclinical and clinical data show that the inherent properties of NKTR-181 reduce its rate of entry into the brain compared to standard mu opioids, regardless of route of administration. NKTR-181 is an investigational medicine and has not been approved by the FDA or any other regulatory agencies.