Researchers say the new formulation could reduce overdose fatalities caused by fentanyl and other synthetic opioids.
The U.S. Food and Drug Administration (FDA) recently authorized SRI to initiate a Phase 1 clinical trial of a new naloxone formulation under an Investigational New Drug (IND) application. The clinical trial will evaluate SRIโs high-dose naloxone formulation for intravenous (IV) and intramuscular (IM) use.
Deaths involving synthetic opioids rose by more than 700% between 2015 and 2022, according to the National Center for Health Statistics. While overdose deaths have begun to decline, fentanyl and other synthetic opioids continue to devastate communities around the country.
To address this critical public health challenge, a team of researchers in SRIโs Biosciences division has developed an injectable formulation of naloxone designed to provide a rapid and sustained reversal of opioid overdose, particularly in cases involving ultra-potent synthetic opioids such as fentanyl, nitazenes, and carfentanil. These substances are increasingly present in the illicit drug supply and have been associated with overdose cases that are difficult to reverse using currently available naloxone products.
Why we need additional tools in our overdose toolkit
โThe current naloxone formulations are all very low dose and theyโre not as effective for the kinds of synthetic opioids that are hitting the market today,โ says Gita Shankar, senior director of the Pharmaceutical Sciences Lab at SRI. โThis medication can help reduce the number of opioid fatalities with a single high-dose naloxone shot that first responders can choose to inject into overdosed victim when the risk of death is high. Unlike autoinjectors, the first responder can be trained to adjust the dose based on the individual.โ
โGiving naloxone in higher doses can reduce a deep overdose more effectively, but itโs not as simple as injecting a larger volume of the existing medication.โ โ Gita Shankar
When someone overdoses on opioids, their breathing can slow or even stop, leading to oxygen deprivation, coma, and death. Naloxone, also known by the brand name Narcan, can reverse these effects by blocking opioid receptors in the brain and displacing any opioids that are binding to those receptors.
โThe problem is that Narcan only lasts about 90 minutes,โ Shankar says. โThen it drops off and the opioids can re-bind to those receptors.โ This can result in renarcotization, a recurrence of overdose symptoms including respiratory depression, and the patient can stop breathing again. โGiving naloxone in higher doses can reduce a deep overdose more effectively, but itโs not as simple as injecting a larger volume of the existing medication,โ Shankar adds.
How SRIโs novel naloxone formulation works
To address the limitations of current overdose protocols, Shankar and her team developed a highly concentrated naloxone formulation that delivers 10 times more naloxone per milliliter than current marketed products. The formulation is optimized for systemic availability and shelf stability, making it more suitable for emergency use in the field.
โFlooding the system with naloxone ensures that more opioid receptors are blocked effectively and that more molecules from deeply binding opioids like fentanyl are displaced,โ says Shankar. โThis significantly reduces the risk of recurrence โ although continuous monitoring is necessary.โ
The researchers have been able to leverage safety studies from other naloxone products to support the clinical development of this formulation. With the clinical trial now underway, the team is actively advancing manufacturing steps to support a rapid path toward a New Drug Application (NDA) following successful trial completion.
โThis is a more effective naloxone formulation with improved systemic availability and product stability on the shelf,โ Shankar says. โIn the hands of emergency responders, it has the potential to address the synthetic opioid overdose crisis head-on and save lives.โ
To learn more about this project or to work with SRI, contact us today.
Effort sponsored by the U.S. Government under Other Transaction number W15QKN-16-9-1002 between the MCDC, and the Government. The US Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon.
The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government.
