3570 The Regulatory Landscape of Products to Treat Opioid Overdose

Abstract

OBJECTIVES/SPECIFIC AIMS: Since 1971, Naloxone has been the only FDA approved opioid antagonist indicated for use after opioid overdose. New formulations of Naloxone have been introduced into the market, including an injectable, auto-injector, and nasal spray. However, Naloxone is short-acting and as such often requires multiple doses and may induce severe withdrawal symptoms. This study examines the regulatory framework to understand the evolution of products indicated to treat opioid overdose and the landscape of therapies in development. Furthermore, this study examines how the Food and Drug Administration (FDA) and other government agencies have approached the opioid crisis. METHODS/STUDY POPULATION: A PubMed search of “naloxone AND opioid overdose” with the filter “humans” was conducted to understand Naloxone’s regulatory framework. The term “naloxone” was searched on the Drugs@FDA: Approved Drug Products database. Additionally, “nalmefene” was searched on ClinicalTrials.gov. To examine the opioid antagonist market landscape, a PubMed search of “opioid antagonist AND opioid overdose” with the filters “humans” and “clinical trial,” and a ClinicalTrials.gov search of “opioid antagonist and opioid overdose,” were conducted. Government agency reports were reviewed and cataloged. RESULTS/ANTICIPATED RESULTS: Preliminary findings suggest a lack of innovation in the development of novel opioid antagonists. Most literature review findings focused on already-marketed Naloxone products, including the original injectable approved in 1971, the 2014 Evzio Auto-Injector, and the 2015 Narcan Nasal Spray (Figure 1). For example, there were 14 results yielded from the FDA approvals database, but none of these results represented a new opioid antagonist molecule. A longer-acting opioid antagonist, Nalmefene injectable, was approved in 1995 but has since been removed from the market due to low sales. Our initial ClinicalTrials.gov search using condition “opioid overdose” and other terms “opioid antagonist”,revealed no new studies being conducted on alternative opioid antagonist treatments for opioid overdose. Findings only focused on the distribution, co-dispensing, intervention, pharmacokinetics/pharmacodynamics (PK/PD) of Naloxone (Figure 2). However, a Google search yielded one new trial with an opioid antagonist by Opiant Pharmaceuticals, almost fifty years after FDA’s approval of Naloxone. A ClinicalTrials.gov search was then performed using the search term “nalmefene” to find whether Opiant Pharmaceuticals’ trial was in the ClinicalTrials.gov database. However, the Opiant trial is phase I, and as such does not require reporting on ClinicalTrials.gov. In 2017, the National Institutes of Health (NIH) launched an initiative for longer-acting opioid antagonist formulations. In 2018, Opiant Pharmaceuticals announced positive phase I results for intranasal Nalmefene. The potential return of Nalmefene in intranasal form may play a significant role in reducing overdoses, especially in cases where a longer-acting opioid antagonist is necessary. Opiant Pharmaceuticals’ trial commenced after the NIH announced their initiative; furthermore, the NIH’s National Institute on Drug Abuse granted the company $7.4 million to further the investigation of this drug. We will continue to research drugs that have previously been studied for the indication of treating opioid overdose in the United States and abroad and catalog them. DISCUSSION/SIGNIFICANCE OF IMPACT: The abuse and misuse of opioids in the United States has caused an epidemic accounting for over 115 opioid-overdose deaths each day, devastating our nation, both socially and economically. The United States spends $78.5 billion annually to combat the misuse of these drugs. Due to the severity of the opioid crisis, efforts to better understand approved therapies and investigational products in development to treat opioid overdose will be of significance moving forward. This research can inform agencies who are developing strategies to reduce opioid overdoses and pharmaceutical product developers about the current opioid antagonist landscape.