Indivior announces the publication of new data on the comparative effectiveness of intranasal (IN) nalmefene (OPVEE 2.7 mg) and IN naloxone (4 mg) in a translational model evaluating the impact of synthetic opioid overdose on respiratory depression and cardiac arrest

• Significant reductions in the incidence of simulated cardiac arrest caused by life-threatening doses of fentanyl or carfentanil were observed after a single IN dose of OPVEE compared to a single IN dose of naloxone.
• In all fentanyl or carfentanil overdose scenarios, the simultaneous administration of four doses of IN naloxone (4 × 4 mg) was necessary to reduce the incidence of simulated cardiac arrest to values ​​close to those obtained with a single dose of OPVEE (3 mg). Modeling predictions among chronic opioid users indicate that the incidence of cardiac arrest following an overdose of intravenous (IV) fentanyl (2.97 mg) decreased by 78% in the absence of intervention at 12% with OPVEE and at 47% with an IN dose of 4 mg of naloxone. .

RICHMOND, Virginia., June 18, 2024 /PRNewswire/ — Indivior PLC (LSE/Nasdaq: INDV) today announced the publication of a modeling study in Frontiers in Psychiatry that predicts that OPVEE (nalmefene) nasal spray (2.7 mg nalmefene, equivalent to 3 mg of nalmefene hydrochloride) would result in greater results. reductions in the incidence of simulated cardiac arrest following overdose from high doses of potent synthetic opioids, compared to a 4 mg dose of IN naloxone.

Model simulations were performed using a validated translational model¹ developed by the Division of Applied Regulatory Sciences of the Center for Drug Evaluation and Research of the United States Food and Drug Administration. In the present study, this translational model was expanded with data from pharmacokinetic and pharmacodynamic studies with OPVEE.^2.3 and IN naloxone pharmacokinetic data.² Simulations were carried out on 2,000 virtual patients. After a 2.97 mg IV dose of fentanyl resulted in a 78% incidence of cardiac arrest in chronic opioid users, a single administration of 4 mg IN naloxone reduced this rate to 47%, while a single dose of IN OPVEE reduced this rate to 12%. . Four simultaneous doses of 4 mg IN naloxone were required to reduce the incidence of cardiac arrest to 17%, comparable to that observed after a single dose of OPVEE (12%).

Simulations in opioid-naïve individuals illustrated the same trend, although a higher incidence of cardiac arrest was predicted in this population due to lack of tolerance to the respiratory effects of opioids. Simulation of an IV overdose of fentanyl (2.97 mg) in opioid-naïve individuals led to a 90% incidence of cardiac arrest, which was reduced to 26% with IN OPVEE and to 68% after 4 mg IN naloxone, respectively.

In the United States, more than 78,200 fatal opioid overdoses were reported in the past year. December 2023of which almost 92% (71,821) are linked to synthetic opioids.⁴ According to the State Unintentional Drug Overdose Reporting System (SUDORS), the percentage of overdose deaths in which naloxone was administered (22% in the United States in 2022)⁵suggests that the naloxone may not have been administered quickly enough or in a sufficient dose.

“This modeling data is relevant given the current overdose epidemic, characterized by a growing prevalence of overdoses from illegally manufactured synthetic opioids, which can be extremely difficult to reverse.⁶,” said Christian HeidbrederPhD, Chief Scientific Officer of Indivior, Inc. “This simulated data serves two purposes. First, they quantify the challenge of effectively reversing a synthetic opioid overdose. Second, these data inform the approach of first responders (e.g., police, fire and rescue personnel, friends and family of the overdose victim) in a community setting that does not benefit from the ventilatory support available in a emergency department, there is a limited window of time before a hypoxic injury becomes irreversible and cardiac arrest occurs; this can happen extremely quickly with fentanyl and other synthetic opioids⁷“.

Similar effects have been observed following opioid overdose simulations using carfentanil, which is 100 times more potent than fentanyl.⁸ These trends remain consistent for both chronic and opioid-naive individuals overdosing on carfentanil.

About OPVEE^®

OPVEE (nalmefene) nasal spray

INDICATION

OPVEE nasal spray is an opioid antagonist indicated for the emergency treatment of known or suspected overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, manifested by respiratory depression and/or of the central nervous system.

OPVEE Nasal Spray is intended for immediate administration as emergency treatment in settings where opioids may be present.

OPVEE Nasal Spray is not a substitute for emergency medical care.

HIGHLIGHTED SAFETY INFORMATION

CONTRAINDICATIONS

Hypersensitivity to nalmefene or any of the other ingredients.

WARNINGS AND PRECAUTIONS

Risk of recurrent respiratory and central nervous system depression: Although the duration of action of nalmefene is as long as that of most opioids, recurrence of respiratory depression is possible. Therefore, keep the patient under continuous monitoring and administer repeated doses of OPVEE using a new nasal spray with each dose, if necessary, in the meantime. emergency medical assistance.

Limited effectiveness with partial agonists or mixed agonists/antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeated doses may be necessary.

Precipitation of severe opioid withdrawal: Use in opioid-dependent patients may precipitate opioid withdrawal. In newborns, opioid withdrawal can be life-threatening if not recognized and properly treated. Monitor progress of opioid withdrawal.

Risk of cardiovascular (CV) effects: Abrupt postoperative reversal of opioid depression may result in adverse CV effects. These events occurred primarily in patients with pre-existing cardiovascular conditions or receiving other medications that may have similar cardiovascular adverse effects. Monitor these patients closely in an appropriate health care setting after use of nalmefene hydrochloride.

Opioid overdose risk linked to attempts to overcome blockade: Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may result in opioid poisoning and death.

SIDE EFFECTS

The most common side effects (incidence of at least 2%) are nasal discomfort, headache, nausea, dizziness, flushing, vomiting, anxiety, fatigue, nasal congestion , throat irritation, rhinalgia, decreased appetite, dysgeusia, erythema and hyperhidrosis.

For more information about OPVEE and complete prescribing information, visit www.opvee.com.

About Individual

Indivior is a global pharmaceutical company dedicated to helping change patients’ lives by developing medicines to treat substance use disorders (SUDs), opioid overdoses and serious mental illnesses. Our vision is that all patients worldwide will have access to evidence-based treatment for chronic diseases and co-occurring SUD disorders. Indivior is dedicated to transforming SUD from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of opioid use disorder treatments, Indivior has a pipeline of product candidates designed to both expand its legacy in this category and potentially treat other chronic diseases and concurrent SUD disorders. Based at United States In Richmond, Virginia, Indivior employs more than 1,100 people worldwide and its product portfolio is available in 37 countries around the world. Visit www.indivior.com to learn more. Connect with Indivior on LinkedIn by visiting www.linkedin.com/company/indivior.

SOURCE Individual PLC