AFQ056 · program
Mavoglurant for Cocaine use disorder
Indications for AFQ056: Cocaine use disorder · Phase 2 Huntington's disease · Discontinued Obsessive-compulsive disorder · Discontinued Fragile X syndrome · Discontinued
Mavoglurant (AFQ056/STP7), an oral mGlu5 negative allosteric modulator, for cocaine use disorder — an indication with no FDA-approved pharmacotherapy. Novartis ran the placebo-controlled Phase 2 (NCT03242928, n=68, sites in Switzerland/Spain/Argentina, completed December 2019): 98 days of mavoglurant bid versus placebo in adults with CUD, with reduced cocaine use versus placebo (also reduced concomitant alcohol use), published in Science Translational Medicine in April 2025. On the strength of these data Novartis licensed worldwide rights to Stalicla SA (January 2023; upfront + equity, up to $270M milestones plus royalties). Stalicla, under a Cooperative Research and Development Agreement with NIDA, completed the last Phase 3-enabling regulatory requirement — a Phase 1 double-blind cocaine/STP7 interaction safety study (NCT06273540, n=21, completed 2024-10-07). Stalicla guided US Phase 3 initiation in 2025 (funded by the US government per its DDI announcement), but as of 2026-08-14 no Phase 3 trial is registered on ClinicalTrials.gov and no Phase 3 start has been announced — the program is recorded at phase_2/active with that slippage explicitly noted, not assumed resolved.
Development timeline
- metPhase 2 full results published in Science Translational Medicine: mavoglurant reduced cocaine use versus placebo in 68 adults with cocaine use disorder (NCT03242928), the evidence base for Stalicla's planned Phase 3.↗
- Trial startedStalicla starts Phase 3-enabling cocaine/STP7 drug-drug interaction study (NCT06273540)
- Program changed hands: Stalicla SA in-licensed worldwide rights to mavoglurant from Novartis for substance-use and neurodevelopmental disorders and announced preparation to advance it into Phase 3 for cocaine use disorder. Phase unchanged — the Phase 3-enabling package (DDI study) was still outstanding.↗
- Phase 2 NCT03242928 completed (primary completion and study completion 2019-12-16). Results — reduced cocaine use versus placebo — were later published in Science Translational Medicine (2025-04-02).
- Novartis Phase 2 NCT03242928 (CAFQ056X2201) started: randomized, blinded, placebo-controlled study of whether AFQ056 reduces cocaine use in adults with cocaine use disorder (n=68 actual).
Readouts
- 2025-04-02ReportedFull resultsmetNCT03242928
Phase 2 full results published in Science Translational Medicine: mavoglurant reduced cocaine use versus placebo in 68 adults with cocaine use disorder (NCT03242928), the evidence base for Stalicla's planned Phase 3. ↗
Clinical trials in Cocaine use disorder
NCT06273540STA-P7-C001Phase 1Completedn=21
Phase 1, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess Potential Interactions Between Intravenous Cocaine and Oral STP7
NCT04771143Phase 1Discontinued
Study to Assess Safety, Tolerability, and Interactions of Cocaine and Oral AFQ056 (WITHDRAWN before first patient — no enrollment)
NCT03242928CAFQ056X2201Phase 2Completedn=68
A Randomized, Subject and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Mavoglurant modified-release oral tablet (twice daily)modified_release The OCD proof-of-concept study (NCT01813019, 2013-2014) dosed AFQ056 twice daily as augmentation on top of a stable SSRI in SSRI-resistant patients. The published report describes mavoglurant modified-release; exact per-arm doses are behind the paywall and CT.gov's arm description does not state milligrams, so no dose figure is asserted. | Oral | Twice daily | — |
Mechanism of action
Selective, non-competitive antagonist (negative allosteric modulator) of the metabotropic glutamate receptor 5 (mGlu5, GRM5), a Gq-coupled class-C GPCR densely expressed on striatal medium spiny neurons. In Huntington's disease the rationale was two-fold: symptomatically, damping striatal mGlu5/glutamatergic signaling was hypothesized to reduce chorea; mechanistically, mGlu5 interacts with mutant-huntingtin-related excitotoxic NMDA signaling. The Phase 2 proof-of-concept tested the anti-choreatic (symptomatic) hypothesis and found no significant reduction in chorea versus placebo.
| Target | Action | Affinity |
|---|---|---|
| mGlu5primaryGRM5 | NAM | —ⓘ |
← Full AFQ056 compound page (identity, identifiers, all indications)
Sources
- Gomez-Mancilla B, et al. Mavoglurant reduces cocaine use in patients with cocaine use disorder in a phase 2 clinical trial. Sci Transl Med. 2025;17(792):eadi4505 — Science Translational Medicine (AAAS) / PubMed
- Mavoglurant (AFQ-056), GtoPdb ligand 7586 — mGlu5 negative allosteric modulator — IUPHAR/BPS Guide to PHARMACOLOGY
- NCT01813019 (CAFQ056A2225) — AFQ056 in OCD Patients Resistant to SSRI Treatment (Phase 2, n=50; TERMINATED at first interim analysis, did not meet primary efficacy objective) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT03242928 (CAFQ056X2201) — Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder (Phase 2, n=68, completed 2019-12-16) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT04771143 — Study to Assess Safety, Tolerability, and Interactions of Cocaine and Oral AFQ056 (Novartis; WITHDRAWN before first patient, n=0) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06273540 (STA-P7-C001) — Phase 1 Double-Blind, Placebo-Controlled Study of Interactions Between Intravenous Cocaine and Oral STP7 (Stalicla, n=21, completed 2024-10-07) — ClinicalTrials.gov (U.S. National Library of Medicine)
- STALICLA signs exclusive in-licensing agreement for late-stage clinical neuropsychiatric and neurodevelopmental disorder treatment (2023-01-09) — Stalicla SA (via GlobeNewswire)