GLP-1 RECEPTOR AGONISTS FOR ALCOHOL USE DISORDER: INDICATION POSITIONING AND HTA/JCA IMPLICATIONS
Author(s)
Mahbouba Boualleg, Bioengineer1, Hend Jdidi, DMD1, Aurélie Millier, PhD2, Lylia Chachoua, PharmD2, Aleksandra Caban, PharmD3.
1Clever-Access, Tunis, Tunisia, 2Clever-Access, Paris, France, 3Clever-Access, Cracow, Poland.
1Clever-Access, Tunis, Tunisia, 2Clever-Access, Paris, France, 3Clever-Access, Cracow, Poland.
OBJECTIVES: Alcohol use disorder (AUD) remains undertreated, and the few approved pharmacotherapies (naltrexone, acamprosate, nalmefene, disulfiram) reach a minority of patients. Evidence that GLP-1 receptor agonists (RAs) may reduce alcohol consumption has prompted several trials. This study maps the indication positioning of the emerging GLP-1 RA pipeline in AUD, considers how these agents differ from established treatments, and explores implications for comparator choice, HTA evidence, and pricing.
METHODS: GLP-1 RA trials in AUD were grouped by treatment objective (reduction in heavy drinking days [HDD] or total consumption, abstinence, maintenance), population, and endpoint. HTA decisions for approved AUD agents (HAS, G-BA, NICE, SMC) were examined alongside candidate PICO structures and an indicative price comparison.
RESULTS: Fifteen trials were identified, but the registrational base is limited: only two (both semaglutide) are completed and published, six are mechanistic or safety, and one (CRAVE) is Phase 3. No two studies aligned simultaneously on treatment objective, population, and endpoint, limiting cross-trial comparability. Most target HDD reduction, an endpoint that supported nalmefene's authorization but was deemed insufficient by HAS. CRAVE alone uses the regulator-endorsed WHO risk-drinking-level reduction, and its readout may prove informative. All trials compare GLP-1 RAs against placebo or sham, not the approved AUD agents, leaving no head-to-head data likely to draw HTA scrutiny. About half require a minimum BMI, supporting a metabolic and addiction value story but narrowing eligibility. No trial targets maintenance of abstinence after detoxification, covered by inexpensive established agents. Incumbents are low-priced, leaving little room between a molecule's diabetes and obesity prices.
CONCLUSIONS: Indication positioning, alongside efficacy, is likely to influence the JCA PICO framework and the HTA outcomes. A WHO risk-drinking-level endpoint with a metabolic-comorbidity rationale may prove comparatively more defensible, but the landscape is still developing, with several pivotal trials ongoing. Continued monitoring of readouts, comparators, and pricing will refine these observations.
METHODS: GLP-1 RA trials in AUD were grouped by treatment objective (reduction in heavy drinking days [HDD] or total consumption, abstinence, maintenance), population, and endpoint. HTA decisions for approved AUD agents (HAS, G-BA, NICE, SMC) were examined alongside candidate PICO structures and an indicative price comparison.
RESULTS: Fifteen trials were identified, but the registrational base is limited: only two (both semaglutide) are completed and published, six are mechanistic or safety, and one (CRAVE) is Phase 3. No two studies aligned simultaneously on treatment objective, population, and endpoint, limiting cross-trial comparability. Most target HDD reduction, an endpoint that supported nalmefene's authorization but was deemed insufficient by HAS. CRAVE alone uses the regulator-endorsed WHO risk-drinking-level reduction, and its readout may prove informative. All trials compare GLP-1 RAs against placebo or sham, not the approved AUD agents, leaving no head-to-head data likely to draw HTA scrutiny. About half require a minimum BMI, supporting a metabolic and addiction value story but narrowing eligibility. No trial targets maintenance of abstinence after detoxification, covered by inexpensive established agents. Incumbents are low-priced, leaving little room between a molecule's diabetes and obesity prices.
CONCLUSIONS: Indication positioning, alongside efficacy, is likely to influence the JCA PICO framework and the HTA outcomes. A WHO risk-drinking-level endpoint with a metabolic-comorbidity rationale may prove comparatively more defensible, but the landscape is still developing, with several pivotal trials ongoing. Continued monitoring of readouts, comparators, and pricing will refine these observations.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HPR8
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Disease
Mental Health (including addiction)