Although still in early-stage testing, Ensysce Biosciences’ formulation has demonstrated the potential to address addiction problems associated with oral oxycodone.
Pictured: Loaded syringe and opioids/iStock, Darwin Brandis
In recent years, oxycodone has accrued a murky reputation.
When first introduced as OxyContin in 1996 by Purdue Pharma, the opioid was heavily marketed as a miracle painkiller. However, with side effects such as euphoria, oxycodone has also become a highly sought substance among drug addicts. In addition, the risk of overdose is ever-present, with death likely if too much oxycodone is consumed at once.
Oxycodone currently comes in various oral formulations such as tablets, capsules and oral solutions. These formulations can be abused by crushing them into a powder that can be inhaled or injected for a more immediate and potent euphoric effect, and opioid addiction continues to be a major problem nationwide. According to the National Institutes of Health, drug overdose deaths involving prescription opioids totaled 16,706 in 2021 in the U.S., while the total number of opioid-related deaths, prescription or otherwise, was 80,411.
While past players in the opioid space, such as Purdue, have faced lawsuits for pushing opioids to the unsuspecting public, pharmaceutical manufacturers have begun attempting to stem abuse—by, for example, developing extended-release oral oxycodone formulations. However, studies have demonstrated that even these formulations can be modified for euphoric effects and therefore continue to be abused.
But there is one company with a product that, while early stage, appears promising in effectively combatting opioid addiction and overdose.
Ensysce’s Abuse-Resistant Tech
Ensysce Biosciences is looking for answers to resolve the prescription drug abuse epidemic. In the pain space, Ensysce is developing its Trypsin-Activated Abuse Protection (TAAP) tamper-proof technology, which can prevent oxycodone and other opioids from working until the drug reaches the small intestine, where the abundance of trypsin will activate the opioid. Because the opioid requires the presence of trypsin to become active, TAAP ensures the formulation will not lead to euphoria if crushed and snorted or injected.
In addition, the company is using a trypsin inhibitor called nafamostat to limit activation with increasing ingestion of the product, thereby setting a maximum limit to the overall effect that can be derived from the drug and protecting against overdose.
In results released in January 2023, Ensysce showed that its Multi-Pill Abuse Resistance technology, along with TAAP in its oxycodone capsule formulation (PF614-MPAR), has safety features that can reduce the emergence of habit-forming behaviors compared to regular oxycodone. And in May 2023, Phase I results demonstrated the effectiveness of the second prong of the technology: when three or more capsules were consumed simultaneously, the drug elicited a maximal response and drug levels even decreased compared to the unprotected PF614 formulation.
Although Ensysce is currently recruiting for more pharmacokinetic trials, there is still a long way to go on the pain front. Phase II and III trials have not yet commenced, so while efficacy is assumed based on previous studies performed by others related to oxycodone as an active ingredient, the efficacy of this formulation has not yet been proven in pain patients. Therefore, Ensysce’s pain products may not hit the market until the latter half of this decade at the earliest.
In addition, given that the pancreas manufactures trypsinogen before the substance enters the small intestine and is converted to trypsin, it is likely that patients will need to have a healthy, functioning pancreas for optimal effect.
Nonetheless, Ensysce’s technology is the most promising seen to date for confronting addiction with a preventative formulation. The company is also working on anti-abuse formulations of other substances, such as amphetamine (used to treat ADHD), though these programs are in preclinical stages. Therefore, keep an eye on Ensysce as its pipeline results start to emerge.
Jia Jie Chen writes analyses focusing on drug development in the biotech and pharma industries for BioSpace. He has a doctorate degree in pharmacy and experiences ranging from biotech equity research to business intelligence analysis. Follow him on LinkedIn.
