Ketamine plus relapse-prevention therapy for severe alcohol use disorder
SVN-001 is in a UK Phase 3 trial, building on a published Phase 2a/b proof of concept. It is the most advanced programme in the Solvonis AUD franchise.
SVN-001 is investigational. It has not been approved by any regulator, and its safety and efficacy have not been established.
How ketamine-based treatment works: it opens a window of plasticity, and psychosocial support is designed to work inside it
Ketamine opens the window; in-clinic relapse-prevention therapy uses it to build healthier responses to urges, triggers and relapse risk. The integrated treatment addresses both the biological and psychosocial dimensions of severe AUD. In SVN-002, at-home digital psychosocial support is designed to play the same role.
Sources: Das et al., Nat Commun 2019;10:5187; Grabski et al., Am J Psychiatry 2022;179(2):152–162. The mechanism summarises current understanding of ketamine pharmacology; the pathway in AUD remains under investigation. NMDA: N-methyl-D-aspartate; AMPA: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF: brain-derived neurotrophic factor; mTOR: mammalian target of rapamycin. Esketamine, the active ingredient of SVN-002, is the S-enantiomer of ketamine and acts at the same NMDA receptor.
A completed, academic-led, investigator-initiated trial in 96 patients with severe AUD
Academic investigators at two UK sites (Exeter and London) ran the trial, funded by the Medical Research Council. It was a proof of concept, not designed for registration. Solvonis is now progressing SVN-001 in Phase 3.
Adults with severe AUD, recently detoxified and abstinent at entry, randomised 1:1:1:1 (166 screened).
Three 40-minute IV infusions, 1 to 3 weeks apart: ketamine 0.8 mg/kg or saline. Seven 1.5-hour sessions of relapse-prevention therapy or alcohol education, timed around each infusion. Follow-up to six months.
What was published: one of two co-primary endpoints met, with more days abstinent on ketamine
One of the two co-primary endpoints was met.
Source: Grabski et al., Am J Psychiatry 2022;179(2):152–162 (design, funding statement, Figures 1 and 2; Table 2; Table S1). The co-primary analysis compared all ketamine with all placebo patients: days abstinent was met; confirmed relapse was not. The trial was not powered for arm-by-arm comparison. Trial name: KARE (Ketamine for Reduction of Alcohol Relapse); NCT02649231, EudraCT 2015-000222-11; recruitment September 2016 to July 2019. 96 adults, 2×2 design; arm means over six months, observed data; reporting time capped at 180 days. Confirmed relapse = one or more heavy drinking days within 180 days (n/N shown; only patients with at least 159 days of data). Pooled comparisons are ketamine versus placebo; the trial was not powered for arm-by-arm comparison or to separate drug and therapy effects.
The same two arms on heavy drinking days (the Phase 3 primary endpoint): 55% fewer over the last two months; post hoc
Weeks 17–24, ketamine plus therapy versus placebo plus education: 0.71 vs 1.55 heavy drinking days a week (10.1% vs 22.2% of days); P=.062. Weeks 17–20 alone: 67% fewer, P=.018. Phase 3 uses these two regimens; its control receives low-dose ketamine, not saline.
Phase 3 (European Medicines Agency, EMA): over 60 g of alcohol in a day for men, 40 g for women.
Phase 2a/b re-analysis: 70 g (men) and 56 g (women).
The EMA lists reduction in heavy drinking days as a primary variable. It is the Phase 3 primary endpoint, tested prospectively over 180 days. These Phase 2a/b figures are post hoc.
Ketamine plus therapy versus placebo plus education: further measures
Sources: Morgan CJA, Nutt DJ, medRxiv, 28 September 2026 (post hoc secondary analysis of the Phase 2a/b trial; not peer-reviewed; nominal unadjusted P values; observed cases; ketamine plus therapy n=20 vs placebo plus education n=23). Professor Nutt is Solvonis’ Chief Scientific Officer. Patients had completed detoxification and were measured 4–6 months after the last infusion. Published comparisons: Grabski et al., Am J Psychiatry 2022 (ketamine plus therapy n=24 vs placebo plus education n=25). EMA, Guideline on the development of medicinal products for the treatment of alcohol dependence, section 4.2.1. Definitions differ: EMA over 60 g (men) and 40 g (women); Grabski et al. relapse over 64.8 g and 52.0 g; Morgan and Nutt heavy drinking days 70 g and 56 g.
Phase 3 tests the same two treatment regimens on the endpoint the EMA recognises
The trial is sponsored by the University of Exeter and co-funded by the National Institute for Health and Care Research (NIHR), the Medical Research Council (MRC) and Solvonis. It is authorised by the MHRA, and has been granted an Innovation Passport under the MHRA’s Innovative Licensing and Access Pathway (ILAP).
The most intensive Phase 2a/b arm.
The least intensive Phase 2a/b arm. Low-dose ketamine replaces saline as an active control that protects the blind.
From the published Phase 2a/b to Phase 3
Sources: MORE-KARE protocol version 9, 12 March 2025 (IRAS 1008179; ISRCTN85955128); MHRA clinical trial authorisation and HRA/REC approval, 2 November 2023; MHRA ILAP Innovation Passport; Solvonis RNS, 13 October 2026; Grabski et al., Am J Psychiatry 2022;179(2):152–162; EMA, Guideline on the development of medicinal products for the treatment of alcohol dependence, section 4.2.1 (2010); Company information. “EMA primary variable” refers to the primary variables the guideline specifies for each treatment goal.
Planned European expansion of the Phase 3
On 13 October 2026, Solvonis announced a memorandum of understanding (MoU) with ICAD, Portugal’s public addiction institute, and clinical partner Panegreen, to assess adding Portuguese trial sites to MORE-KARE, the UK Phase 3 trial of SVN-001 for severe alcohol use disorder.
The MoU does not create a binding commitment to proceed with Portuguese trial participation. Any participation remains subject to sponsor and funder agreement and the required approvals.
The EMA’s guideline on alcohol dependence lists reduction in heavy drinking days (over 60 g a day for men, over 40 g for women) as a primary variable. The Phase 3 primary endpoint is the number of heavy drinking days over 180 days, using the EMA thresholds.
Proposed EU sites are intended to generate EU data on that endpoint, to support potential UK and EU marketing authorisation applications after readout.