Oxecta (oxycodone) / Assertio, Acura Pharma - LARVOL DELTA

A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: University of Utah | Recruiting ➔ Completed | N=300 ➔ 100 | Trial completion date: Jul 2021 ➔ Jan 2023 | Trial primary completion date: Jul 2021 ➔ Jan 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Opioids for pain. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Addiction (Opioid and Alcohol) • Pain

Comparison table: Some oral/transdermal opioid analgesics. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Pain

Are Opioids Needed After ACL Reconstruction (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: Emory University | Recruiting ➔ Completed

Trial completion

Drug Companies Test New Booster on Eight Mice and Zero Humans, FDA Approves It Anyway - "Before the FDA's expert panel could even meet to discuss vaccines for children under 5, for example, the White House's COVID czar, Ashish Jha, publicly announced a precise date for when they would become available....'That's just not an acceptable basis for drug or vaccine authorization,' Dr. Vinay Prasad...told me....'You can just have a free market where you can have whatever choice you want,' he said. The purpose of the FDA, by contrast, is 'to shield us from making very, very bad choices.'"

Media quote • Regulatory • Novel Coronavirus Disease

NanaBis™ an Oro-buccal Administered delta9-Tetrahydrocannabinol (d9-THC) & Cannabidiol (CBD) Medicine for the Management of Bone Pain From Metastatic Cancers (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Medlab Clinical | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Aug 2023 ➔ Feb 2024

Monotherapy • Trial completion date • Trial primary completion date • Musculoskeletal Pain • Oncology • Pain • Solid Tumor

Transversus Abdominis Plane Block in Microsurgical Breast Recon w/Abdominal Free Flap in Breast CA (clinicaltrials.gov) - P3; N=120; Completed; Sponsor: Stanford University; Recruiting ➔ Completed; Trial completion date: Mar 2020 ➔ Jun 2021

Trial completion • Trial completion date

Are Opioids Needed After ACL Reconstruction (clinicaltrials.gov) - P4; N=90; Recruiting; Sponsor: Emory University; Not yet recruiting ➔ Recruiting; Trial completion date: Apr 2021 ➔ Nov 2022; Trial primary completion date: Apr 2021 ➔ Nov 2022

Clinical • Enrollment open • Trial completion date • Trial primary completion date

[VIRTUAL] The Dorsal Peduncular Cortex is a Cortical Master of Opioid Withdrawal (ACNP 2020) - "These data thoroughly characterize the DP, a highly novel and unique opioid-responsive cortical region. The DP shows enriched expression of the µ opioid receptor, and selectively deleting this receptor in the DP reverses the hedonic valence of oxycodone, creating aversion rather than reward. Most interestingly, electrophysiological and single-nuclei sequencing data indicate that this receptor is expressed on glutamatergic output neurons, and anatomical tracing experiments show these neurons projecting to hindbrain regions known to be implicated in addiction and stress responses."

Addiction (Opioid and Alcohol) • Alzheimer's Disease • CNS Disorders • Pain • Psychiatry • Substance Abuse • Tobacco Addiction • Synaptophysin

Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward. (PubMed, Addict Biol) - "However, other MOR-mediated behaviors were unaffected, including oxycodone-induced analgesia. These data reveal that MOR-mediated regulation of glutamate transmission is a critical component of opioid reward."

Journal • Addiction (Opioid and Alcohol) • Pain

Development and impact of prescription opioid abuse deterrent formulation technologies (Drug Alcohol Depend) - "Reviewed is the FDA recent approval of a product label describing the abuse deterrent characteristics of OxyContin® (physical barrier formulation), and the FDA determination that studies were insufficient for an Opana® (physical barrier) ADF label. Additional reviewed marketed OpAs with ADF technologies include: Suboxone® and Embeda® (opioid agonist/antagonist combinations), Oxecta® (aversion technology), and Nucynta® (physical barrier)....The outcomes of the recent ADF labeling applications for OxyContin® (Tier 3 approval) and Opana® (non-approval) suggest that the threshold for ADF labeling will be appropriately high."

Review • Pain

Acura Pharmaceuticals provides update on opioid product licensed to Pfizer (Marketwire) - Pfizer is advancing the commercialization of Oxecta; Acura is eligible to receive tiered royalties ranging from 5% to 25% on net sales of Oxecta; The royalties commence on first anniversary of first commercial sale of Oxecta which Acura does not expect to occur during 2011

License agreement update • Pain

Orange Book: Approved drug products with therapeutic equivalence evaluations: Newly added patent (FDA) - Newly added patent in Orange Book for Oxecta.

Patent • Pain

Intranasal abuse potential of an IR oxycodone formulation (AAPM-Clinical 2011) - P=NA, N=40; In nondependent recreational opioid users, results of the study suggest that crushed IRO-A tablets may have a lower intranasal abuse potential than crushed IR oxycodone (IRO) tablets because of the functional excipients in potential of crushed oxycodone tablet (IRO-A)

Clinical data • Pain

Bioequivalence of IRO-A, IRO-A/niacin, and a branded oxycodone (AAPM-Clinical 2011) - P1, N=40; IRO-A (oxycodone with inactive functional excipients to prevent abuse) was bioequivalent to commercially available immediate-release oxycodone (IRO), as well as IRO-A (oxycodone and niacin); Because of its unique aversion technology IRO-A (oxycodone with inactive functional excipients to prevent abuse) provides an alternative approach to conventional immediate-release oxycodone therapy that may reduce potential intranasal and intravenous abuse

P1 data • Pain

Acura Pharma: Annual Report 2012 (Acura) - Anticipated patent expiry in US for pain in 2025

Anticipated patent expiry • Pain

Dose proportionality and the effects of food on bioavailability of an immediate-release oxycodone hydrochloride tablet designed to discourage tampering and its relative bioavailability compared with a marketed oxycodone tablet under fed conditions: A sing (Clin Ther) - P1, N=35; NCT01530542; Plasma levels of oxycodone in immediate-release oxycodone hydrochloride formulation (IRO-A) tablets were compatible with proportional single-dose pharmacokinetics from 5 to 15 mg under fasted conditions; Administration of IRO-A with food suggested increased overall bioavailability relative to fasting conditions and a reduction in peak systemic exposure of oxycodone that is not expected to be clinically significant

P1 data • Pain

Acura Pharmaceuticals provides update on opioid product licensed to Pfizer (Marketwire) - Acura Pharmaceuticals announced today that it has been informed by Pfizer that Oxecta (oxycodone) tablets are now commercially available; Acura will receive tiered royalties ranging from 5% to 25% on net sales of Oxecta commencing on the first anniversary of the first commercial sale of Oxecta

Anticipated milestone payment • Commercial launch • Pain

Oxycodone-Mediated Activation of the Mu Opioid Receptor Reduces Whole Brain Functional Connectivity in Mice. (PubMed, ACS Pharmacol Transl Sci) - "In conclusion, we demonstrate that oxycodone reduces brain communication in a MOR-dependent manner, and establish a preliminary whole-brain FC signature of oxycodone. This proof-of-principle study provides a unique platform and reference data set to test other MOR opioid agonists and perhaps discover new mechanisms and FC biomarkers predicting safer analgesics."

Journal • Preclinical • MRI

Dopamine DR antagonist VK4-116 attenuates oxycodone self-administration and reinstatement without compromising its antinociceptive effects. (PubMed, Neuropsychopharmacology) - "In contrast, VK4-116 had little effect on oral sucrose self-administration. Taken together, these findings indicate a central role for D3Rs in opioid reward and support further development of VK4-116 as an effective agent for mitigating the development of opioid addiction, reducing the severity of withdrawal and preventing relapse."

Journal

Strengths and weakness of atypical opioids - "My colleague, Richard Rauck, MD...discussed strengths and weakness of three atypical opioids: tramadol, tapentadol, and buprenorphine....Dr. Rauck and I presented the results of a recent study that examined the effect of four doses of buccal buprenorphine film - 300 ug, 450 ug, 600 ug, or 900 ug - on respiratory drive. Using a hypercapnic model to induce respiratory drive, all four doses of buccal buprenorphine film failed to produce a decrease in respiratory drive compared to a placebo, as measured by a change in minute ventilation. This is in contrast to a significant decrease in minute ventilation with 60 mg of immediate-release oxycodone."

Are postoperative opioids in opioid-naïve patients necessary (Dermatology Advisor) - P=NA, N=NA; "Panelists agreed that non-opioid analgesics were appropriate as first-line pain management after a dermatologic procedure unless contraindicated. Acetaminophen 1 g every 8 hours and/or ibuprofen 400 mg every 4 hours were recommended to provide appropriate postoperative pain relief. In cases in which opioids are reasonably needed for adequate pain management, the panelists agreed that acetaminophen and/or nonsteroidal medications should be combined with opioid analgesics."

Clinical data

Opioid-induced toxic leukoencephalopathy: A case report and review of the literature. (PubMed, Heliyon) - "Reports demonstrate a range of outcomes that include patients who died to those with no residual neurologic deficits. This review of reported pediatric cases of opioid-induced leukoencephalopathy highlights the importance of early neurosurgical intervention for prevention of devastating outcomes."

Clinical • Journal • Review

Zyla Life Sciences reports third quarter 2019 financial results (PRNewswire) - "Zyla Life Sciences...today reported financial results for the third quarter ended September 30, 2019, including net sales from commercial products: SPRIX® (ketorolac tromethamine) Nasal Spray, the SoluMatrix® products, VIVLODEX® (meloxicam), TIVORBEX® (indomethacin) and ZORVOLEX® (diclofenac)), INDOCIN® (indomethacin) suppositories, INDOCIN® oral suspension and OXAYDO® (oxycodone HCI, USP) tablets for oral use only –CII....Net product sales were $22.4 million for the three months ended September 30, 2019 compared to $8.2 million for the three months ended September 30, 2018. The increase was largely due to the addition of the five acquired products at the end of January 2019."

Sales

Identification of the Dorsal Peduncular Area as a Highly Novel Regulator of Opioid Reward (ACNP 2019) - "Currently, all FDA-approved medications for opioid dependence are partial (e.g. buprenorphine) or full (e.g. methadone) agonists at the μ opioid receptor, and thus serve as replacement therapies... These data thoroughly characterize the DP, a highly novel and unique opioid-responsive cortical region. The DP shows enriched expression of the µ opioid receptor, and most interestingly, electrophysiological and single-nuclei sequencing data indicate that this receptor is expressed on glutamatergic output neurons. Furthermore, the connectivity profile of the DP makes it a highly likely candidate to be an important regulator of opioid reward, analgesia, and withdrawal."