The opioid epidemic continues to wreak havoc in the United States, with over 107,000 deaths from opioid overdoses in 2022 alone, driven largely by synthetic opioids like fentanyl. This crisis has spurred the need for innovative solutions to prevent and treat opioid misuse and overdose. Greg Sturmer, CEO and Co-Founder of Elysium Therapeutics, is at the forefront of this effort. Under his leadership, Elysium is developing advanced strategies, such as the O2P hydrocodone, designed to reduce the risk of misuse and overdose while ensuring effective pain management. Today, he discusses the objectives and designs behind their clinical trials for this groundbreaking formulation.
Moe: What is the design and objective behind the clinical trials for Elysium’s O2P hydrocodone?
Greg Sturmer: Our Phase I human proof of concept study for O2P hydrocodone was designed to go beyond the conventional parameters of early clinical trials, which typically focus primarily on safety. By involving 93 subjects, our study was able to robustly test not only safety but also the efficacy of O2P hydrocodone in managing moderate to severe pain. Furthermore, we investigated its potential to prevent overdose, a critical concern with opioid medications. The trial demonstrated that O2P hydrocodone could be administered less frequently, with dosing intervals extended to 12 and 24 hours, thus reducing the need for frequent medication and minimizing the risk of misuse.
In addition to establishing safety and efficacy, our study sought to understand how well the drug could control exposure levels during potential overdose scenarios. The results were promising, showing a reduction in exposure by approximately 50% even when up to 16 pills were taken. This indicates that O2P hydrocodone has a built-in mechanism to limit the absorption of the drug beyond safe thresholds, which is crucial for preventing fatal overdoses. These findings highlight the potential of O2P as a safer alternative for pain management, capable of delivering effective relief while significantly mitigating the risk associated with opioid overdose.
Moe: How does O2P hydrocodone’s mechanism of action prevent overdose?
Greg Sturmer: O2P hydrocodone employs a revolutionary molecular delivery system that tricks the body into recognizing the drug as food. This deception is pivotal because it necessitates using a specific digestive enzyme to activate the drug, thereby controlling its release and absorption. The crux of this system’s overdose prevention mechanism lies in its enzyme inhibitor. This inhibitor is cleverly integrated into the molecular structure and progressively diminishes the enzyme’s ability to activate the drug once a threshold—such as a 10-pill dosage—is exceeded. This self-regulating feature ensures that even if an excessive amount is ingested, the biological activation of the opioid is curtailed, effectively preventing the risk of a lethal overdose.
O2P hydrocodone distinguishes itself by using chemical strategies rather than physical barriers. While many existing formulations focus on making opioids difficult to manipulate for injection or inhalation—using hard-to-crush pills or gels that resist extraction—O2P takes a fundamentally different approach. By embedding specific chemical properties within the drug itself, O2P significantly reduces the risk of overdose through oral administration, the most common method of opioid abuse. This approach allows the medication to maintain its therapeutic effectiveness while preventing the release of harmful levels when taken in excess. In stark contrast to abuse-deterrent opioid formulation approaches, O2P opioids stand out by offering dual protection—effective pain management and robust safeguarding against all prevalent forms of opioid misuse.
Moe: What challenges were encountered during the Phase I trial of O2P?
Greg Sturmer: The initiation of the Phase I trial for O2P hydrocodone faced significant logistical challenges, primarily due to the complications introduced by the COVID-19 pandemic. These included delays in manufacturing the drug and hurdles in obtaining the FDA’s approval to begin the trial. These issues were compounded by the widespread disruptions to supply chains and regulatory operations during the pandemic, posing a complex set of obstacles that needed careful navigation to keep the project on track. Despite these initial setbacks, our commitment to advancing this crucial study remained undeterred, emphasizing our resolve to bring this innovative pain management solution to trial.
Once we overcame the early challenges and the trial was underway, our collaboration with MEDPACE, a clinical research organization in Ohio, proved instrumental in efficiently managing the trial’s execution. MEDPACE’s expertise facilitated rapid recruitment and smooth operation of the trial processes, ensuring we could gather comprehensive data on O2P’s efficacy and safety. This partnership was crucial in maintaining the momentum of the study amid ongoing external challenges, allowing us to focus on evaluating our product under rigorous scientific scrutiny. The successful management of these phases kept the trial on schedule and provided invaluable insights essential for the next stages of development.
Moe: How does Elysium’s SOOPR Rescue Agent initiative differ from existing treatments like Narcan?
Greg Sturmer: Elysium’s SOOPR Rescue Agent initiative represents a significant advancement in addressing the specific challenges posed by the modern opioid epidemic, particularly the rise in the use of synthetic opioids like fentanyl in pill form. Unlike traditional treatments such as Narcan (naloxone), which are optimized for rapid onset to counteract the immediate effects of opioid overdose, SOOPR is engineered to provide a longer duration of action. This extended protection is crucial because fentanyl, when consumed in pill form, metabolizes differently, often with a slower onset and a more prolonged effect than other opioids. SOOPR’s formulation is tailored to this profile, offering sustained antidotal activity that is more aligned with the duration of fentanyl’s effects, thereby providing more comprehensive coverage during an overdose event.
Furthermore, SOOPR addresses a critical gap in overdose intervention that Narcan and similar agents cannot fill. While Narcan works effectively against rapid-onset opioids and is invaluable in emergency scenarios, its effects wear off quickly, which can be inadequate for the persistent presence of fentanyl in the system, leading to the potential for re-narcotization and reassertion of potentially lethal respiratory depression. SOOPR’s innovative approach ensures that its protective effects persist as long as the opioid remains active, reducing the need for multiple antidote administrations and enhancing the safety and efficacy of emergency response. This prolonged efficacy is particularly advantageous in non-hospital settings, empowering first responders and bystanders with a more effective tool in combating the deadly consequences of fentanyl overdoses.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
