Nektar Therapeutics announced the U.S. Food and Drug Administration (FDA) has filed and accepted for review the company's New Drug Application (NDA) for NKTR-181 for the treatment of chronic low back pain in adult patients new to opioid therapy. NKTR-181 is a new molecular entity (NME) and the first analgesic opioid molecule to exhibit a low incidence of specific CNS-mediated side effects, such as euphoria, through the targeted alteration of brain-entry kinetics. The NDA is expected to be assigned a PDUFA (Prescription Drug User Fee Act) target action date of May 28, 2019 by the FDA.
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Nektar's NDA submission is supported by an extensive 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.
NKTR-181 is an investigational medicine and has not been approved by the FDA or any other regulatory agencies. While the NDA submission for NKTR-181 has been accepted for review by the FDA, such acceptance does not mean that NKTR-181 will be approved by the FDA.
NKTR-181 is the first long-acting, selective full mu-opioid receptor agonist designed to provide potent pain relief, without the inherent high levels of euphoria, which contribute to abuse and addiction with 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 abuse potential 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.