XpIrx: overview

Dramatically reduce the supply and abuse of leftover opioids

  • Problem – Unused Opioids Fuel the Epidemics: Previously, the ONDCP reported that the opioid epidemic is being fueled by an unlikely source – unused prescription opioids in Americans’ medicine cabinets. Studies indicate that 33% - 50%, or even more, of prescribed opioids remain unused by patients to whom they are prescribed, which, for hydrocodone-containing pills alone, represents enough pills to encircle the earth added to American’s medicine cabinets on an annual basis. One of the most significant aspects enabling the illegal diversion of unused prescription opioids is their extended shelf life. Current opioid drugs lose only ~1% of their potency per year (a ~70-year potency half-life). As a result, unused prescription opioids remain highly potent, and therefore susceptible to abuse and diversion, long after the time intended for their prescribed use, and their indicated expiration date, have lapsed. The (i) enormous number of opioid prescriptions written annually, (ii) the robust chemical stability of opioid agonists, and (iii) the high percentage of leftover pills, have resulted in the widespread “stockpiling” of unused opioids for personal abuse (often among teenage initiate abusers), distribution to friends or family, and/or illicit sale for profit over an extended time.
  • Elysium’s Solution – XpiRx™ Technology: Elysium has innovated a novel molecular deactivation “XpiRx” technology designed to offer first-in-class diversion-resistance to effectively curb the widespread stockpiling, diversion, abuse, and overdose of unused prescription opioids, even by the most common route of abuse, oral ingestion. XpiRx opioids are designed to “force” opioids to lose their potency shortly after their prescribed-use period has lapsed. XpiRx provides the following unprecedented features:

During the prescribed-use period:

  • Equi-analgesic to comparators – offers effective pain relief
  • Abuse-resistant via non-oral routes of administration

After the prescribed-use period: 

  • Minimal/No opioid agonist effects - similar to placebo
  • Irreversibly “abuse-proof” via ALL routes
  • Highly unattractive to chronic opioid abusers
  • Protects against fatal overdose
  • Applicable to IR & ER oral opioids, ~90% of all prescription opioids 

NIDA (NIH) has awarded us a grant to advance XpiRx through IND-enabling studies. We have identified our lead and backup candidates for upcoming non-clinical and clinical studies. We believe that this technology could become commercially available in the 2021-timeframe.

O2P™ (ORAL OVERDOSE PROTECTION): OVERVIEW

Protects Against the Primary Route of Abuse

  • Problem – Prescription Opioid Abuse is a Deadly Epidemic: According to the CDC, from 2000 to 2014, nearly half a million persons in the United States died from drug overdoses. In 2014, there were approximately one and a half times more drug overdose deaths in the United States than deaths from motor vehicle crashes. Opioids, primarily prescription pain relievers and heroin, are the main drugs associated with overdose deaths. Further, the rate of drug overdose deaths involving natural and semi-synthetic opioids (e.g., morphine, oxycodone, and hydrocodone) was the highest among all opioid-related overdose deaths, and has increased 9% from 2013 to 2014. While IMS Health data reveals that there has been a 12% decrease in opioid prescriptions since 2012, fewer prescriptions has not resulted in fewer deaths.
  • Problem – Current Technologies Do Not Address the Primary Route of Abuse (Co-ingestion of multiple pills): Published data indicates that ingestion is the most prevalent route of abuse – in the case of immediate-release opioids, nearly 90% of individuals entering substance-abuse treatment reported the oral route of administration as their primary mode of abuse. While the most prevalent route of abuse is the oral route, current formulation- and molecular-based “tamper-resistant” technologies are designed to resist abuse primarily via non-oral routes (e.g., inhalation and injection).  Unfortunately, these approaches can easily be thwarted by straightforward extraction techniques, and fail to adequately address the key issues of (i) diversion, (ii) oral abuse, and (iii) potentially lethal oral overdose.
  • Elysium’s Solution – O2P™ (Oral Overdose Protection): In stark contrast to our competitors that employ physics to develop formulations that make it more difficult for hardcore abusers to tamper with opioids to inhale and/or inject them, Elysium has employed chemistry to create a new class of opioid molecules that offer superior tamper-resistance, while also protecting against oral overdose (i.e., simultaneous ingestion of multiple pills) – the primary route of abuse. Our O2P opioids auto-attenuate the systemic exposure of the active opioid as the number of co-ingested pills increases. A key benefit of our technology is that these protections are embedded in each pill at the molecular level. Unlike naloxone rescue kits that must be in the right hands at the right time to rescue someone who has overdosed, O2P pills will effectively prevent the overdose from occurring in the first place. 

Our O2P opioids are designed to provide the following unprecedented features:

  • Resistant to ALL routes of abuse
  • Effective oral overdose protection over a relevant dose range that eliminates the dose-proportional “reward” abusers enjoy with all currently marketed prescription opioids
  • Protection against fatal oral overdoses
  • Broadly applicable to immediate-release and extended-release opioids for acute and chronic use, respectively. We are initially applying our O2P technology to immediate-release hydrocodone and oxycodone products as these represent the clear majority of prescribed opioids, and they are overwhelmingly abused via the oral route. 

With the support of NIH/NIDA, we have  demonstrated in vivo proof of concept for this program (see below), and have identified lead compounds for progression to non-clinical and clinical studies. The first product could be on the market in the 2021-timeframe.