Indivior PLC announced results from a pharmacodynamic study demonstrating that OPVEE® rapidly reverses opioid-induced respiratory depression, which is the major cause of deaths due to opioid overdose. The study, "Reversal of opioid-induced respiratory depression in healthy volunteers: comparison of intranasal nalmefene and intranasal naloxone", was published in the Journal of Clinical Pharmacology (Reversal of Opioid-Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone - Ellison - The Journal of Clinical Pharmacology - Wiley Online Library) and is the first head-to-head comparison examining the effects of 2.7 mg intranasal (IN) nalmefene (OPVEE) and 4 mg IN naloxone on opioid-induced respiratory depression. This study was a part of the OPVEE development program and reviewed by the FDA as part of the approval process.

This study met the primary endpoint by demonstrating that OPVEE reversed the respiratory depression produced by remifentanil, a potent synthetic opioid related to fentanyl, within the first 5 minutes following administration. Both OPVEE and IN naloxone produced a time-dependent reversal of the opioid-induced respiratory depression 2.5 to 20 minutes post administration. Point estimates favored OPVEE, demonstrating non-inferiority and superiority to naloxone.

After OPVEE administration, subjects' minute ventilation (a measure of the amount of air that enters the lungs per minute) reached approximately 95% of the pre-opioid baseline within 5 minutes and maintained this robust reversal through the initial 20-minute monitoring period. By contrast, naloxone required 20 minutes to restore respiration to levels equaling those observed 5 minutes after OPVEE. There is an urgent need for rapid acting reversal agents because synthetic opioids, like fentanyl, impair breathing and reduce oxygen levels to vital organs like the brain more rapidly than other opioids such as morphine and heroin.

Following administration of OPVEE, subjects' minute ventilation (MV), a measure of how much a person is breathing, increased by an average of 5.75 L/min at 5 minutes, the study's primary endpoint. Intranasal naloxone produced a mean increase of 3.01 L/min at 5 minutes post-administration, and 20 minutes was required to produce an increase in MV similar to that observed 5 minutes after OPVEE.