nalmefene intranasal (OPNT003) / Indivior - LARVOL DELTA

Post-marketing Surveillance of Intranasal Nalmefene: Prevalence and Clinical Relevance of Precipitated Withdrawal. (PubMed, Cureus) - " Post-marketing surveillance data suggest that the risk of precipitated withdrawal with IN nalmefene is low in real-world settings. These findings support the continued deployment of IN nalmefene as a life-saving intervention while underscoring the importance of ongoing pharmacovigilance to monitor for emerging safety signals."

Journal • P4 data • Addiction (Opioid and Alcohol) • CNS Disorders

Reversal of a Synthetic Opioid Overdose: Insights From a Validated Translational Model. (PubMed, Neuropharmacology) - "In the absence of intervention, simulations using various intravenous doses of fentanyl and carfentanil predicted an incidence of cardiac arrest ranging from 18% to 90% in chronic opioid users and from 40% to 96% in opioid naïve subjects...Across those simulations, intranasal nalmefene was generally more effective than intranasal naloxone in reducing brain hypoxia duration. These findings illustrate both the relative effectiveness of nalmefene and naloxone in reversing a synthetic opioid overdose and the importance of rapid intervention."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders

Translational Modeling as a Tool to Evaluate the Effectiveness of Nalmefene in a Community Setting: A Critical Perspective. (PubMed, Clin Pharmacol Ther) - No abstract available

Journal

Synthetic opioids have disrupted conventional wisdom for treating opioid overdose. (PubMed, Drug Alcohol Depend Rep) - "Reports using this model demonstrated the naloxone tools (2 mg intramuscular and 4 mg intranasal) used by many first responders can result in an unacceptable loss of life following a synthetic opioid (fentanyl, carfentanil) overdose...Furthermore, simultaneous administration of four doses of intranasal naloxone was needed to reduce the incidence of cardiac arrest to levels approaching those produced by a single dose of intranasal nalmefene. These data are consistent with evidence that synthetics have indeed disrupted conventional wisdom in the treatment of opioid overdose."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Psychiatry

Editorial: Discovery, development and implementation of improved options for treating opioid overdose in the synthetic opioid era. (PubMed, Front Psychiatry) - No abstract available

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Psychiatry • Vascular Neurology

Comparison of intranasal naloxone and intranasal nalmefene in a translational model assessing the impact of synthetic opioid overdose on respiratory depression and cardiac arrest. (PubMed, Front Psychiatry) - "(Clin Pharmacol Ther 2022) to evaluate the effectiveness of intramuscular (IM) naloxone...Simulations using this validated translational model of opioid overdose demonstrate that a single dose of IN nalmefene produces clinically meaningful reductions in the incidence of cardiac arrest compared to IN naloxone following a synthetic opioid overdose. These findings are especially impactful in an era when >90% of all opioid overdose deaths are linked to synthetic opioids such as fentanyl."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Mood Disorders • Psychiatry

Comparative Effectiveness of Intranasal Naloxone and Nalmefene in a Translational Model Assessing Reversal of Cardiac Arrest Induced by Synthetic Opioid Overdose (CPDD 2024) - "(Clin Pharmacol Ther 2022;112(5):1020-32) to evaluate the effectiveness of intramuscular naloxone in reversing the respiratory depression effects of fentanyl and its derivatives... Using a validated translational model of opioid overdose, IN nalmefene resulted in a clinically meaningful reduction in the incidence of cardiac arrest compared to IN naloxone at doses of synthetic opioids that led to a 50-90% incidence of cardiac arrest in the absence of antagonist treatment."

HEOR • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Psychiatry

Reversal of Opioid-Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone. (PubMed, J Clin Pharmacol) - P1 | "An open-label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil-induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT04828005)...Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders • Psychiatry

Comment on: Can Intranasal Nalmefene Reduce the Number of Opioid Overdose Deaths? (PubMed, Clin Pharmacol Drug Dev) - No abstract available

Journal • Addiction (Opioid and Alcohol) • CNS Disorders

Pharmacokinetic Properties of an FDA-approved Intranasal Nalmefene Formulation for the Treatment of Opioid Overdose. (PubMed, Clin Pharmacol Drug Dev) - P1 | "There were no sex differences in the pharmacokinetic properties of either IN or IM nalmefene. In an era when almost 90% of opioid overdose deaths have been linked to high-potency synthetic opioids, the ability to rapidly deliver high concentrations of nalmefene could represent an important tool for reducing both morbidity and mortality."

FDA event • Journal • PK/PD data • Addiction (Opioid and Alcohol) • CNS Disorders

Pharmacodynamic Evaluation of Intranasal Nalmefene (clinicaltrials.gov) - P1 | N=84 | Completed | Sponsor: Opiant Pharmaceuticals Inc | Recruiting ➔ Completed | N=60 ➔ 84

Enrollment change • Trial completion

"$OPNT Opiant Pharmaceuticals Announces Completion of Rolling NDA Submission for OPNT003, Nasal Nalmefene, for Opioid Overdose https://t.co/6Wg8qPtcVG" (@stock_titan)

NDA • Addiction (Opioid and Alcohol) • CNS Disorders

"Indivior capitalized on the fall of Opiant's share price throughout the year to add a near-approval nasal formulation of nalmefene to its portfolio. https://t.co/cj5rq1OSxE" (@FiercePharma)

"$OPNT Opiant Pharmaceuticals and Aptar Pharma Expand Long-Term Collaboration for the Manufacture of Unidose Nasal Spray for OPNT003, Nasal Nalmefene https://t.co/m7onSJDmlt" (@stock_titan)

Pharmacokinetic Evaluation of Intranasal Nalmefene Using Three Dosing Regimens (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Opiant Pharmaceuticals Inc

New P1 trial

Pharmacokinetic Evaluation of Intranasal Nalmefene (clinicaltrials.gov) - P1; N=68; Completed; Sponsor: Opiant Pharmaceuticals Inc; Recruiting ➔ Completed

Clinical • Trial completion

Treatment of overdose in the synthetic opioid era. (PubMed, Pharmacol Ther) - "Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs...Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era"."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Infectious Disease • Novel Coronavirus Disease

Pharmacodynamic Evaluation of Intranasal Nalmefene (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: Opiant Pharmaceuticals Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Pharmacodynamic Evaluation of Intranasal Nalmefene (clinicaltrials.gov) - P1; N=54; Not yet recruiting; Sponsor: Opiant Pharmaceuticals Inc

New P1 trial

Pharmacokinetic Evaluation of Intranasal Nalmefene (clinicaltrials.gov) - P1; N=68; Recruiting; Sponsor: Opiant Pharmaceuticals Inc

Clinical • New P1 trial

Opiant Pharmaceuticals Announces First Patient Dosed in Confirmatory Pharmacokinetic Study Assessing OPNT003, Nasal Nalmefene, for the Treatment of Opioid Overdose (GlobeNewswire) - "Opiant Pharmaceuticals...announced the dosing of the first patient in a confirmatory pharmacokinetic ('PK') study for OPNT003, nasal nalmefene, for the treatment of opioid overdose. Results from the study are anticipated June 2021....The Company plans to file a 505(b)(2) New Drug Application for OPNT003 with the U.S. Food and Drug Administration by the end of 2021."

NDA • Trial status • Addiction (Opioid and Alcohol)

Countermeasures for preventing and treating opioid overdose. (PubMed, Clin Pharmacol Ther) - "This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: 1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; 2) methocinnamox, a novel opioid receptor antagonist; 3) covalent naloxone nanoparticles; 4) serotonin (5-HT) receptor agonists; 5) fentanyl-binding cyclodextrin scaffolds; 6) detoxifying biomimetic "nanosponge" decoy receptors; and 7) antibody-based strategies. These strategies could also be applied to treat opioid use disorder (OUD)."

Journal • Review • Addiction (Opioid and Alcohol) • Allergy • CNS Disorders • Immunology • Infectious Disease

Opiant Pharmaceuticals announces contract with Biomedical Advanced Research and Development Authority for up to $4.6 million to accelerate development of OPNT003, nasal nalmefene, for treatment of opioid overdose (GlobeNewswire) - "Opiant Pharmaceuticals, Inc...announced that it has entered into a multi-year contract with potential funding up to a maximum of approximately $4.6 million, with the Biomedical Advanced Research and Development Authority (BARDA)...to accelerate Opiant’s development of OPTN003...for the treatment of opioid overdose....Expect to begin the pivotal pharmacokinetic study required for approval of OPNT003 by the U.S. Food and Drug Administration in 2019...The BARDA contract...provides approximately $611,000 for the project from now through September 30, 2019..."

Financing • Licensing / partnership • New trial • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Opiant Pharmaceuticals announces receipt of first tranche from National Institutes of Health grant for development of OPNT003, intranasal nalmefene, for treatment of opioid overdose (GlobeNewswire) - “Opiant Pharmaceuticals…announced today that it has received the first tranche of $500,000 from the previously awarded grant of approximately $7.4 million from the National Institutes of Health’s National Institute on Drug Abuse for the development of OPNT003…for the treatment of opioid overdose….The NIH grant includes approximately $2.6 million to be funded for the period ending March 31, 2019, with the balance to be funded over the subsequent two years.”

Grant • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Opiant Pharmaceuticals announces first quarter 2020 financial results and corporate update (GlobeNewswire) - "Separately, we have agreed with the FDA on the design of a short PD study in healthy volunteers that we believe will enhance the clinical profile of OPNT003. As we progress towards our regulatory filing for OPNT003, we are also having to factor into our timeline the impact of prolonged COVID-19 related travel restrictions on our equipment engineers in Europe. Based on these collective modifications to our OPNT003 development program, our NDA filing is now likely to occur in early 2021.”"

NDA • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry