Indivior PLC announced the dosing of the first subject with INDV-2000 in a Phase 2 double-blind, placebo controlled, randomized, dose-ranging study to assess the safety and efficacy of INDV-2000 over 3 months in treatment-seeking individuals with Opioid Use Disorder (OUD) (NCT06384157). The purpose of this proof-of-concept study is to measure safety and efficacy and to determine the dose-response relationship for INDV-2000 in participants with moderate to severe OUD who are treatment-naïve, have recently initiated or completed short-term medically supervised opioid withdrawal with transmucosal (TM) buprenorphine, and are interested in transitioning to a non-opioid treatment. This milestone is another step in Indivior's mission to develop new treatment options for patients with OUD and other substance use disorders.

With the support of an NIH-HEAL grant (1R01DA043898-01A1) titled "Clinical Evaluation of INDV-2000 (C4X3256), a Non-Opioid, Highly Selective Orexin-1 Receptor Antagonist for the Treatment of Opioid Use Disorder" the study was initiated for the clinical development of INDV-2000, a potent and selective oral orexin-1 receptor (OX1R) antagonist, with demonstrated activity in rodent models of addiction and a safety profile suitable for therapeutic administration in clinical studies.1 More recently, animal studies also have shown that selective antagonism of the OX1R can reduce heroin intake and oxycodone self-administration2 and reduce the consumption of synthetic opioids including remifentanil3 and fentanyl. The orexin-A and orexin-B neuropeptides are agonists of the orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R), respectively. The OX1R and OX2R are thought to play differential physiological roles with the OX1R mainly involved in motivation and reward and the OX2R in the modulation of the sleep/wake cycle and energy homeostasis.3 The completion of clinical Phase 1 Single Ascending Dose (NCT04413552) and Multiple Ascending Dose (NCT04976855) studies happened after an end-of-Phase 1 meeting with the FDA on November 3, 2023, paving the way for the preparation and initiation of this clinical Phase 2 proof-of-concept (PoC) study.

Opioid use disorder (OUD) involves disruption of brain circuits engaged in reward, decision-making, learning, and self-control. The magnitude of OUD worldwide highlights the need for novel molecular entities ultimately translating into new medications for the treatment of OUD. In the United States, among people aged 12 or older in 2022, 3.2% (or 8.9 million people) misused opioids in the past year.