Indivior Begins Phase 2 Study of INDV-2000 for Opioid Use Disorder

Indivior PLC has commenced a Phase 2 clinical trial to evaluate INDV-2000, an investigational non-opioid treatment for moderate to severe Opioid Use Disorder (OUD). This double-blind, placebo-controlled study aims to assess the safety and efficacy of INDV-2000 over a period of three months. INDV-2000 works through the orexin pathway, which animal studies have shown plays a crucial role in substance use disorders. Selective antagonism of the Orexin-1 receptor has been found to reduce self-administration of opioids and synthetic opioids like fentanyl and remifentanil.

The trial, which has started dosing its first participant, seeks to determine the dose-response relationship for INDV-2000 in participants who are either new to treatment or have recently completed short-term medically supervised opioid withdrawal with transmucosal buprenorphine. Participants will be randomized to either the INDV-2000 group or a placebo group and will receive the treatment in conjunction with transmucosal buprenorphine for the first seven days. From day eight onward, INDV-2000 or placebo will be administered as a standalone treatment. The randomized treatment period spans three months, concluding either at the last study visit or when participants initiate buprenorphine rescue therapy due to relapse.

This trial is a critical step in Indivior's mission to develop new treatment options for patients with OUD and other substance use disorders. Supported by an NIH-HEAL grant, this study is part of the clinical development of INDV-2000, a potent and selective oral orexin-1 receptor antagonist. Previous animal studies have shown that selective antagonism of the Orexin-1 receptor can reduce the intake of opioids like heroin and oxycodone, as well as synthetic opioids.

INDV-2000 provides a unique opportunity to address unmet needs in OUD treatment by potentially offering the first non-opioid orexin-targeted therapy, as stated by Christian Heidbreder, Chief Scientific Officer at Indivior. By providing a non-opioid alternative, INDV-2000 aims to broaden the spectrum of care available for OUD treatment.

OUD involves the disruption of brain circuits related to reward, decision-making, learning, and self-control. Given the prevalence of OUD, which affected 3.2% of Americans aged 12 or older in 2022, there is a pressing need for novel treatments. Dr. Heidbreder emphasized the importance of developing more treatment options as the opioid epidemic continues to escalate, highlighting Indivior’s commitment to expanding both opioid and non-opioid treatment options.

Indivior is a global pharmaceutical company focused on developing medicines for substance use disorders, opioid overdose, and serious mental illnesses. Headquartered in Richmond, VA, the company employs over 1,100 individuals globally and offers a portfolio of products in 37 countries. Indivior is dedicated to transforming substance use disorders from a global crisis into a recognized and treated chronic disease, with a pipeline of product candidates aimed at addressing various chronic conditions and co-occurring disorders.

The Phase 2 study's primary objectives are to measure the safety and efficacy of INDV-2000 and to establish its dose-response relationship in participants with moderate to severe OUD. The study design involves a randomized, dose-ranging approach to ensure comprehensive assessment over the three-month treatment period. This trial follows the completion of Phase 1 studies, which included Single Ascending Dose and Multiple Ascending Dose assessments, and an end-of-Phase 1 meeting with the FDA, paving the way for the initiation of this Phase 2 proof-of-concept study.

In summary, INDV-2000 represents a novel approach to treating OUD, potentially offering a non-opioid alternative that targets the orexin pathway. This trial marks an important step toward expanding the range of therapeutic options available for individuals struggling with opioid use disorder.