Opioid with 'Overdose Protection' Formulation Wins FDA Breakthrough Designation

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The FDA has granted breakthrough therapy designation to PF614-MPAR, an investigational “next-generation opioid” designed both to deter opioid abuse and to limit oral overdose potential, according to a press release from manufacturer Ensysce Biosciences.¹

The novel agent is designed to deliver optimal pain relief at prescribed doses while also mitigating the possibility of overdose, either accidental or intentional, by “‘shutting down’ opioid release if too much active drug is consumed,” according to the company.¹ The drug combines PF614, an oxycodone prodrug developed by Ensysce, with nafamostat, a protease inhibitor that works in the gut.² Ensysce describes the technology as “tamper-proof” explaining that the analgesic component only becomes active after oral administration brings it into contact with the digestive enzyme trypsin, while the nafamostat component helps prevent overdose via its trypsin-inhibiting properties.² The combination, Ensysce has said, “reduces the ability of recreational users to chew, crush and snort, or manipulate and inject to change the opioid release profile.”²

The company cites the most recent data from the Centers for Disease Control and Prevention indicating that nearly 2 opioid-related overdoses occur in the US every hour.¹ “[Breakthrough therapy designation (BTD)] facilitates our ability to expedite our programs through the approval processes in an efficient manner, with rolling review of both programs,” said Lynn Kirkpatrick, PhD, Ensysce chief executive officer.¹ “We believe our goal of bringing the ‘next generation' of analgesics for severe pain to those in need is becoming a reality.”¹

FDA breakthrough therapy designation facilitates the process of generating the evidence required to support approval, according to Ensysce. It includes the elements of a fast-track designation as well as “intensive guidance” to help ensure optimal efficiency of the drug development program, the company said.¹

Separately the company announced that Ensysce CCO Geoff Birkett will present a poster on PF614-MPAR at the Annual NIH Helping to End Addiction Long-term (HEAL) Initiative Scientific Meeting, scheduled for February 7-8, in Bethesda, MD.³ The poster is entitled “PF614-MPAR: A novel trypsin activated abuse protected (TAAP) extended-release oxycodone prodrug with overdose protection.” The investigational PF614-MPAR is the company’s lead drug under its oral overdose protection platform, Multi-Pill Abuse Resistance.³

“The Ensysce team is pleased with the exceptional data we were able to generate for our MPAR platform and our lead agent, PF614-MPAR,” Birkett said in a press release.³ “The U.S. opioid crisis has not been impacted by a new approach to address abuse for over the last two decades. Ensysce intends to change that with what we believe are disruptive platforms, TAAP and MPAR. We also believe our safer medications will address the growing issue of patients’ lack of access to analgesics to treat severe pain, a situation caused by the opioid crisis.”³

1. Ensysce Biosciences announces FDA breakthrough therapy designation granted for PF614-MPAR. News release. Encysce Bioscences. January 23, 2024. Accessed January 29, 2024. https://ir.ensysce.com/news/press-releases/detail/139/ensysce-biosciences-announces-fda-breakthrough-therapy

2. Ensysce Biosciences announces initiation of final state of groundbreaking overdose protection phase 1 study. News release. Ensysce Biosciences. January 25, 2034. Accessed January 20, 2024. https://ir.ensysce.com/news/press-releases/detail/95/ensysce-biosciences-announces-initiation-of-final-stage-of

3. Ensysce Biosciences to present groundbreaking oral overdose protection for opioids at 5th annual NIH HEAL meeting. News release. Ensysce Biosciences. January 25, 2024. Accessed January 29, 2024. https://ir.ensysce.com/news/press-releases/detail/140/ensysce-biosciences-to-present-groundbreaking-oral-overdose