The FDA has accepted for review a new drug application (NDA) for NKTR-181 from Nektar Therapeutics (NKTR) for the treatment of chronic low back pain in adult patients new to opioid therapy, explains John McCamant, biotech sector expert and editor of The Medical Technology Stock Letter.
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 date of May 28, 2019 by the FDA.
Nektar's NDA submission is supported by 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 non-cancer pain, who are new to opioid therapy, as well as those who are experienced with opioid therapy.
The submission also includes 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 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.
The FDA acceptance of the ‘181 NDA is a significant milestone for Nektar and their wholly-owned pipeline as it further de-risks this very valuable asset.
In our view, ‘181 remains under-appreciated by Wall Street and is not being reflected in the company’s valuation. A novel pain drug that can avoid the euphoria associated with highly abused opioids has multi-billion dollar potential as it would be a major tool to help decrease America’s opioid crisis.
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