(M-073) Exposure-Response Analyses for Monthly Buprenorphine Extended-Release (BUP-XR) in Patients with Opioid Use Disorder and Frequent Fentanyl Use
Monday, October 20, 2025
7:00 AM - 5:00 PM MDT
Location: Colorado A
Lauren Lohmer, PhD – Indivior, Inc; Mark Greenwald – Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine; Celine Laffont – Indivior, Inc
Director, Quantitative Clinical Pharmacology Indivior, Inc, United States
Disclosure(s):
Lauren Lohmer, PhD: No financial relationships to disclose
Objectives: Following changes in the illicit opioid landscape, this study aimed to evaluate buprenorphine exposure-response relationships in patients with opioid use disorder (OUD) and high-risk opioid use defined by self-report of injecting opioids, using high doses (≥500 mg intravenous heroin equivalent), and/or using potent synthetic opioids such as fentanyl.
Methods: Longitudinal illicit opioid use and craving data were analyzed in 500 patients with moderate-to-severe OUD and high-risk opioid use who received extended-release buprenorphine (BUP-XR) over Weeks 1 to 38 (NCT04995029). Following administration of two 300-mg doses given 1 week apart, patients were randomized to receive 8 maintenance doses of 100 mg or 300 mg every 4 weeks. At baseline, most patients (78%) used fentanyl, and the main route of opioid use varied (29% injection). Emax mixed-effects logistic regression models were developed to analyze past-week opioid abstinence (yes/no, based on urine drug screens and self-reports) and current opioid craving (treated as ordinal). Treatment retention was modeled using time-to-event analysis.
Results: Despite overall lower opioid abstinence in this high-risk population compared to previous analyses assessing 2015 clinical data[1], buprenorphine EC50 (plasma concentration reaching half maximal effect) was consistent with prior estimate (1.2 ng/mL), indicating maximal efficacy was reached at 2-3 ng/mL in most patients. Frequent fentanyl use (daily or ≥14 times/week) was associated with higher EC50, suggesting benefits of the 300-mg maintenance dose in this patient subpopulation. As in prior analyses, time to treatment discontinuation was well described by a Gompertz hazard model, and opioid craving score >20 (on a 100-mm visual analogue scale) was associated with higher dropout rate. Retention in treatment was good, irrespective of BUP-XR maintenance dose, with earlier dropout at younger age. Opioid craving was influenced by race and age.
Conclusions: These analyses provide new insights into buprenorphine efficacy and optimal dosing regimen in OUD patients with frequent fentanyl use.
The results in this abstract have been previously presented in part at the Canadian Society of Addiction Medicine Conference 16-18 October 2025.
Citations: [1] Laffont CM, Ngaimisi E, Gopalakrishnan M, Ivaturi V, Young M, Greenwald MK, Heidbreder C. Buprenorphine exposure levels to optimize treatment outcomes in opioid use disorder. Frontiers in Pharmacology. 2022 Nov 18;13:1052113.
