Indivior Announces the Publication of New Data on the Comparative Effectiveness of Intranasal (IN) Nalmefene (OPVEE 2.7mg) and IN Naloxone (4 mg) in a Translational Model Assessing the Impact of a Synthetic Opioid Overdose on Respiratory Depression and Cardiac Arrest

• Large reductions in the incidence of simulated cardiac arrest caused by potentially lethal doses of fentanyl or carfentanil were observed following a single IN dose of OPVEE compared to a single dose of IN naloxone.
• Across scenarios of fentanyl or carfentanil overdoses, simultaneous administration of four doses of IN naloxone (4×4 mg) was needed to reduce the incidence of simulated cardiac arrest to values approaching those obtained with a single dose of OPVEE (3mg). Modeling predictions in chronic opioid users indicate that the incidence of cardiac arrest following an intravenous (IV) fentanyl overdose (2.97 mg) decreased from 78% in the absence of intervention to 12% with OPVEE and 47% with a 4 mg IN dose of naloxone.

RICHMOND, Va., June 18, 2024 /PRNewswire/ -- Indivior PLC (NASDAQ:INDV) today announced the publication of a modeling study in Frontiers in Psychiatry that predicts OPVEE (nalmefene) nasal spray (2.7 mg nalmefene, equivalent to 3 mg of nalmefene hydrochloride) resulted in larger 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 Science in the US Food and Drug Administration's Center for Drug Evaluation and Research. In the present study, this translational model was further expanded with data from pharmacokinetic and pharmacodynamic studies with OPVEE^2,3 and IN naloxone pharmacokinetic data.² Simulations were conducted in 2000 virtual patients. Following an IV dose of 2.97 mg fentanyl that 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 needed to lower the incidence of cardiac arrest to 17% which was comparable to that observed following 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 given the lack of tolerance to the respiratory effects of opioids. Simulation of an IV fentanyl overdose (2.97 mg) in opioid naïve individuals led to an incidence of cardiac arrest of 90%, which was reduced to 26% with IN OPVEE and to 68% after 4 mg IN naloxone, respectively.

More than 78,200 fatal opioid overdoses in the US were reported in the one year ending December 2023, with almost 92% (71,821) 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 US in 2022)⁵, suggests that naloxone might not have been administered fast enough or at sufficient dosage.

"These modeling data are relevant considering today's overdose epidemic with increasing prevalence of overdoses from illicitly manufactured synthetic opioids, which can be extremely difficult to reverse⁶," said Christian Heidbreder, PhD, Chief Scientific Officer, Indivior, Inc. "These simulated data serve two purposes. First, they quantify the challenge of effectively reversing a synthetic opioid overdose. Second, these data inform the approach for 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 an Emergency Department. Without adequate ventilatory support, there is a limited time window before hypoxic injury is irreversible and cardiac arrest occurs; this can happen extremely rapidly with fentanyl and other synthetic opioids⁷."

Similar effects were 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 naïve 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, as manifested by respiratory and/or central nervous system depression.

OPVEE nasal spray is intended for immediate administration as emergency therapy 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 to any of the other ingredients.

WARNINGS AND PRECAUTIONS

Risk of Recurrent Respiratory and Central Nervous System Depression: While the duration of action of nalmefene is as long as most opioids, a recurrence of respiratory depression is possible, therefore, keep patient under continued surveillance and administer repeat doses of OPVEE using a new nasal spray with each dose, as necessary, while awaiting emergency medical assistance.

Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses may be required.

Precipitation of Severe Opioid Withdrawal: Use in patients who are opioid dependent may precipitate opioid withdrawal. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated. Monitor for the development of opioid withdrawal.

Risk of Cardiovascular (CV) Effects: Abrupt postoperative reversal of opioid depression may result in adverse CV effects. These events have primarily occurred in patients who had preexisting CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of nalmefene hydrochloride.

Risk of Opioid Overdose from Attempts to Overcome the Blockade: Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death.

ADVERSE REACTIONS

Most common adverse reactions (incidence at least 2%) are nasal discomfort, headache, nausea, dizziness, hot flush, vomiting, anxiety, fatigue, nasal congestion, throat irritation, rhinalgia, decreased appetite, dysgeusia, erythema, and hyperhidrosis.

For more information about OPVEE and the full Prescribing Information visit www.opvee.com.

About Indivior

Indivior is a global pharmaceutical company working to help change patients' lives by developing medicines to treat substance use disorders (SUD), opioid overdose and serious mental illnesses. Our vision is that all patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of SUD. 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 on its heritage in this category and potentially address other chronic conditions and co-occurring disorders of SUD. Headquartered in the United States in Richmond, VA, Indivior employs more than 1,100 individuals globally and its portfolio of products is available in 37 countries worldwide. Visit www.indivior.com to learn more. Connect with Indivior on LinkedIn by visiting www.linkedin.com/company/indivior.

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