loxicodegol (NKTR-181) / Nektar Therap - LARVOL DELTA

In vivo and in vitro Characterization of a Partial Mu Opioid Receptor Agonist, NKTR-181, Supports Future Therapeutic Development. (PubMed, Front Pain Res (Lausanne)) - "This signaling profile is coupled with a slower onset of antinociception and limited drug-seeking behavior in comparison with oxycodone. Together with its known long half-life and slow blood-brain barrier transport, these data suggest that NKTR-181 could be further studied as a pharmacotherapeutic treatment modality for OUD."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Pain • Substance Abuse

A Phase 2 Study To Assess The Efficacy, Tolerability, And Safety OF NKTR-181 In Subjects With Chronic OA Knee Pain (clinicaltrials.gov) - P2; N=296; Completed; Sponsor: Nektar Therapeutics; N=213 ➔ 296

Enrollment change • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

SUMMIT-07: Efficacy and Safety Study of NKTR-181 in Opioid-Naive Subjects With Low Back Pain (clinicaltrials.gov) - P3; N=1189; Completed; Sponsor: Nektar Therapeutics; N=610 ➔ 1189

Clinical • Enrollment change • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Assessment of potentially abuse-related events in two phase 3 studies of NKTR-181, a novel opioid analgesic, using the MADDERS® system (Misuse, Abuse, and Diversion Drug Event Reporting System). (PubMed, Curr Med Res Opin) - "The MADDERS® system discerns potentially abuse-related events and identified low rates of withdrawal and a low risk of abuse potential, diversion or addiction associated with NKTR-181 in phase 3 trials."

Journal • P3 data • Addiction (Opioid and Alcohol) • Back Pain • Lumbar Back Pain • Oncology • Pain • Substance Abuse

Nektar doses first subjects in phase 1 clinical study evaluating NKTR-192, a new short-acting opioid molecule for the treatment of acute pain (PRNewswire) - Nektar Therapeutics announced that the first subjects were dosed last week in a P1 clinical study to evaluate the pharmacokinetics and safety of NKTR-19, the company's novel short-acting mu-opioid analgesic candidate; Nektar plans to advance NKTR-181 into P2 clinical development in chronic pain patients in mid-2012

Anticipated P2 trial • P1 update • Pain

New oral opioid analgesic NKTR-181 demonstrates analgesic response in cold pressor test in healthy subjects (AAPMed 2013) - Abstract #115; P=NA, N=15; “Although NKTR-181 was rapidly absorbed and detected in plasma within 15 min, the maximum central effect was consistently observed 2 to 3 hours after NKTR-181 Tmax, indicating a significant time lag between plasma and CNS”

Clinical data • Pain

Nektar Therapeutics' CEO presents at UBS Global Healthcare Conference (Transcript) (SeekingAlpha) - "So we will be coming forth this summer with both efficacy and abuse liability studies for NKTR-181..."

Anticipated clinical data • Pain

NKTR-181: A Novel Mu-Opioid Analgesic with Inherently Low Abuse Potential. (PubMed, J Pharmacol Exp Ther) - "NKTR-181 was distinguishable from oxycodone by its reduced abuse potential in self-administration and progressive ratio break point models, with behavioral effects similar to those of saline, as well as reduced CNS side effects as measured by the modified Irwin test. The in vitro and in vivo studies presented here demonstrate that NKTR-181 is the first selective mu-opioid agonist to combine analgesic efficacy and reduced abuse liability through the alteration of brain-entry kinetics."

Journal • Addiction (Opioid and Alcohol) • Biosimilar • CNS Disorders • Pain

Nektar initiates second phase 1 clinical study evaluating NKTR-181, a novel opioid molecule, for treatment of chronic pain (PRNewswire) - Second P1 expected to be completed by the end of 2011; P2 development in patients with chronic pain planned for 2012; Results from the first P1 study will be presented at the 2011 American Academy of Pain Management (AAPM) Annual Clinical Meeting on Sep 21, 2011

Anticipated P1 data presentation • Anticipated P1 study completion • Anticipated P2 trial • Pain

Efficacy, safety, and tolerability of NKTR-181 in patients with moderate to severe chronic low-back pain: A Phase 3 study (PAINWeek 2017) - "In patients with moderate to severe chronic low-back pain, NKTR-181 administered at 100 to 400 mg twice daily was associated with statistically significant analgesia throughout 12 weeks of randomized, double-blind treatment. There were statistically significantly greater number of subjects experiencing at least a 30% and 50% reduction in pain and reporting their condition as improved or very much improved in the NKTR-181 treated subjects compared to placebo. NKTR-181 was well tolerated and exhibited a relatively favorable safety profile, including a low incidence of CNS-related AEs including those of sedation, daytime sleepiness and dizziness compared to conventional opioid therapies."

Clinical • P3 data • CNS Disorders • Pain

Nektar Therapeutics: J.P.Morgan Healthcare Conference (Nektar Therapeutics) - "NKTR-181: Phase 2 Human Abuse Liability Trial"; "NKTR-181 has significantly lower "drug high" ratings than oxycodone (p < 0.0001)"

P2 data • Pain

Nektar announces positive clinical data from second phase 1 clinical study of NKTR-181, a novel opioid analgesic molecule to treat chronic pain (PRNewswire) - P1, N=60; Pupillometry data from the study demonstrated that NKTR-181's centrally-mediated opioid effects are dose-dependent and that the molecule enters the brain slowly, which could reduce the euphoria and other CNS side effects; NKTR-181 was also well-tolerated over the entire 8-day dosing period in the study at all doses evaluated; P2 study anticipated in mid 2012

P1 data • Pain

Nektar Therapeutics: Investor and Analyst R&D Day (Nektar Therapeutics) - “Results of Phase 2 EERW efficacy study”; “Most patients in the study were on background NSAIDs”; “During randomized phase, no placebo rebound and study did not meet primary endpoint”; “In the subset analysis of the 25 patients that did not take background NSAIDs, a rebound was observed in placebo patients”

P2 data • Pain

Nektar Therapeutics: J.P.Morgan Healthcare Conference (Nektar Therapeutics) - Anticipated initiation of P3 efficacy SUMMIT-12 trial in chronic low back pain in H2 2016

Anticipated new P3 trial • Pain

Nektar Therapeutics reports financial results for the second quarter of 2016 (PRNewswire) - " 'Our Phase 3 study of NKTR-181 in patients with chronic low back pain has now completed enrollment and is on track to have topline data in the first quarter of 2017.' "

Anticipated P3 data: top line • Demo Pain • Pain

Nektar Therapeutics: Jefferies London Healthcare Conference 2016 (Nektar Therapeutics, Jefferies 2016 London Healthcare Conference) - Anticipated initiation of P3 pivotal human abuse liability trial in pain in Q4 2016; Anticipated top-line data from P3 trial in pain in H1 2017

Anticipated new P3 trial • Anticipated P3 data: top line • Demo Pain • Pain

Nektar Therapeutics: Jefferies London Healthcare Conference 2016 (Nektar Therapeutics, Jefferies 2016 London Healthcare Conference) - Anticipated initiation of P3 pivotal human abuse liability trial in pain in Q4 2016; Anticipated top-line data from P3 trial in pain in H1 2017

Anticipated new P3 trial • Anticipated P3 data: top line • Demo Pain • Pain

Nektar Therapeutics: Investor and Analyst R&D Day (Nektar Therapeutics) - “NKTR-181 Achieves Maximum Pupil Diameter Reduction Comparable to Oxycodone”

P1 data • Pain

Nektar Therapeutics: Q4 FY 2015 Results (Nektar Therapeutics) - Anticipated initiation of second P3 SUMMIT-12 trial in opioid experience patients in H1 2017; Anticipated regulatory submission for pain in early 2019

Anticipated new P3 trial • Anticipated regulatory • Pain

Summit-07: A randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain. (PubMed, Pain) - "In patients with moderate-to-severe CLBP, NKTR-181 demonstrated significant analgesic efficacy and a favorable safety/tolerability profile, with a low incidence of CNS AEs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal."

Clinical • Journal

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain. (PubMed, Pain Med) - "NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP."

Clinical • Journal • P3 data

Preclinical Assessment of the Analgesic Pharmacology of NKTR-181 in Rodents. (PubMed, Cell Mol Neurobiol) - "NKTR-181 had a slower onset, but similar efficacy, to morphine in the models studied supporting reduced abuse potential while maintaining analgesic effect in comparison with current opioids."

Journal • Preclinical

A Study Using Functional Magnetic Resonance Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users. (clinicaltrials.gov) - P1; N=8; Terminated; Sponsor: Nektar Therapeutics; N=24 ➔ 8; Recruiting ➔ Terminated; Trial primary completion date: Mar 2020 ➔ Dec 2019; Sponsor Decision

Clinical • Enrollment change • Trial primary completion date • Trial termination • MRI

Pharmaceutical and narcotic analgesics (Maekyung Media Group) - "...three pipelines of narcotic analgesics did not receive positive feedback at ADCOM, hosted by the Anesthetic and Analgesic Drug Products Advisory Committee...drug oxycodegol (NKTR-181) of Nektar herapeutics, a chronic low back pain treatment...No clinical trials were conducted, and all 27 consultants declined to approve because of concerns about drug abuse. Esteve pharmaceuticals 'tramadol and celecoxib combination drug E-58425 were found to be equal to 13:13..."

Non-US regulatory

FDA approves cocaine nasal spray (Pain News Network) - "FDA advisory committees have taken a dim view of opioid medications recently, soundly rejecting new drug applications for the 'opioid of the future' oxycodegol and a new extended-release version of oxycodone."

FDA event