Opioid analgesics play an important role in the management of moderate to severe pain. However, abuse, misuse, overdose, and deaths from these products have resulted in a major public health issue.¹ Prescription medications, particularly opioid analgesics, are prone to being abused through physical and chemical manipulation for the purpose of increasing drug concentration in the bloodstream in order to accelerate or intensify their effects. These formulations may be altered by crushing them then swallowing, snorting, smoking, or dissolving them in a solution and injecting.^1,2

The abuse potential of a substance is mediated by the magnitude and rate of onset of its psychoactive effects.^2,3 Drug likeability and reinforcing effects are therefore enhanced in drugs with certain pharmacokinetic and pharmacodynamic attributes, such as high peak plasma concentrations (ie, greater C_max) and rapid rise in plasma concentrations (ie, shorter T_max) (see Figure).^2,3 Abusers may manipulate tablets and alter route of administration to increase C_max and/or reduce T_max.²

A 2011 report by the US Centers for Disease Control and Prevention reported that drug-related deaths became the leading cause of accidental death in the United States in 2009.⁴ According to the National Center for Health Statistics, 41% of drug-related deaths in 2011 involved the use of opioid analgesics.⁵ A 2013 research report prepared by the Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services (SAMHSA) estimated that 4.5 million (1.7%) Americans aged 12 years or older had used prescription pain relievers for nonmedical purposes in the previous month.⁶ The total costs of prescription drug abuse were estimated to be as high as $72.5 billion annually for public and private healthcare payers in the United States, according to a 2013 report in the American Journal of Managed Care.⁷

In reaction to the increasing costs and other consequences, such as drug overdose and death, of widespread prescription opioid abuse, the US government and several of state legislatures have introduced, and in some cases have enacted, legislation and regulations intended to encourage the development and adoption of abuse-deterrent formulations of opioid analgesics. In January 2013, the US Food and Drug Administration (FDA) issued draft guidance that for the first time outlined a regulatory pathway for the approval of drugs with abuse-deterrent claims in their product label.¹

In line with FDA guidance prioritizing development of opioid analgesics with abuse-deterrent properties,¹ Egalet has made the development of pain treatments that deter the abuse and misuse of prescription medications its number-one priority. Egalet’s marketed product OXAYDO™ (oxycodone HCl, USP) Tablets for oral use only - CII is designed to discourage abuse associated with snorting, and SPRIX^® (ketorolac tromethamine) Nasal Spray offers non-opioid treatment for patients who require analgesia at the opioid level. By offering a non-opioid option like SPRIX, opioid-level pain can be treated without the potential for abuse seen with non–abuse-deterrent opioids. In addition, Egalet’s proprietary Guardian™ Technology is being employed to develop a pipeline of late-stage, opioid-based candidate products specifically designed to deter abuse. The lead programs, Egalet-001, an abuse-deterrent, extended-release, oral morphine formulation, and Egalet-002, an abuse-deterrent, extended-release, oral oxycodone formulation, are entering phase 3 clinical development for the management of pain severe enough to require daily, around-the-clock opioid treatment and for which alternative treatments are inadequate.