Imbrium Therapeutics Submits Investigational NDA for Potential Treatment of Alcohol Use Disorder

An investigational new drug application was submitted to the FDA for sunobinop (Imbrium Therapeutics LP), which is a potential treatment of moderate-to-severe alcohol use disorder (AUD). Sunobinop is an investigational, first-in-class oral compound designed to bind to and activate nociception/orphanin-FQ peptide receptor (NOP), which is expressed in the central and peripheral nervous system.¹

“Over the past several years, the data collected to date in our sunobinop development program has supported this potent, partial, and selective agonist as a potential treatment approach for AUD and other serious conditions,” Julie Ducharme, BPharm, MSc, PhD, vice president and chief scientific officer of Purdue Pharma, said in a news release.¹

According to a study published in Clinical Pharmacology in Drug Development, NOP shares similarities in structure with mu, kappa, and delta opioid receptors; however, there have been differences in various functions. There is no measurable affinity for mu- or delta-opioid receptors and has a 1000-fold lower affinity for kappa receptors, making it impossible for opioids to bind to NOP. However, it functions as an inhibitory neurotransmitter, which makes it an important pharmacological target for the development of therapies for substance use disorder, according to the authors.²

NOP has been investigated as a potential therapeutic target for chronic cough, pain, sleep, anxiety, depression, Parkinson disease, addiction, hypertension, interstitial cystitis/bladder syndrome (IC/BPS), and overactive bladder (OAB).²

Sunobinop is currently being evaluated for AUD as well as OAB IC/BPS. Preclinical studies have shown the activation of NOP in AUD models, which reinforces the effect of ethanol in humans. In other studies, sunobinop has shown improvements in sleep measures.¹

The company plans to conduct a 2-part, randomized, double-blind, placebo-controlled study to evaluate the effect of sunobinop given at bedtime on alcohol consumption as well as on alcohol craving. The study will include 240 patients with moderate-to-severe AUD who are seeking treatment, according to a news release.¹

In a study published by The Journal of Clinical Investigation, investigators examined the potential of sunobinop’s role in NOP and the sleep/wake cycle in rats and human patients. Safety, tolerability, and pharmacokinetics of 18 healthy individuals and 22 patients with insomnia disorder were investigated.³

In the healthy subjects, the drug demonstrated rapid absorption after oral administration across 3 mg to 30 mg doses, exhibiting a half-life of approximately 2.1 to 3.2 hours. For those with insomnia, the primary end point of sleep efficiency was high after dosing with sunobinop 10 mg compared with the placebo in 91.4% and 79.8% of patients, respectively. Investigators also found the drug-effect difference between the 2 treatments was 11.8%.³

Furthermore, the drug showed a reduction in latency to persistent sleep, less wake after sleep onset, and fewer nighttime awakenings, according to the authors. Sunobinop was also well tolerated in both sets of patients, with no deaths, serious adverse events, or discontinuations due to AEs. The most commonly reported treatment-related AEs included fatigue, euphoria, and dizziness in health patients and somnolence in those with insomnia.³

REFERENCES

1. Imbrium Therapeutics Submits Investigational New Drug Application to Evaluate Sunobinop for the Potential Treatment of Alcohol Use Disorder. News release. Imbrium Therapeutics LP. August 5, 2024. Accessed August 6, 2024. https://www.businesswire.com/news/home/20240805846833/en/Imbrium-Therapeutics-Submits-Investigational-New-Drug-Application-to-Evaluate-Sunobinop-for-the-Potential-Treatment-of-Alcohol-Use-Disorder

2. Cipriano A, Kapil RP, Zhou M, et al. Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants. Clin Pharmacol Drug Dev. 2024;13(7):790-800. doi:10.1002/cpdd.1394

3. Whiteside GT, Kyle DJ, Kapil RP, et al. The nociceptin/orphanin FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia. J Clin Invest. 2024;134(1):e171172. Published 2024 Jan 2. doi:10.1172/JCI171172