AFQ056 · program
Mavoglurant for Huntington's disease
Indications for AFQ056: Cocaine use disorder · Phase 2 Huntington's disease · Discontinued Obsessive-compulsive disorder · Discontinued Fragile X syndrome · Discontinued
Novartis's Phase 2 proof-of-concept of mavoglurant (AFQ056) for chorea in Huntington's disease (NCT01019473, CAFQ056A2207): a multi-centre, randomized, double-blind, placebo-controlled, parallel-group, multiple-oral-dose-titration study (n=44 actual, started November 2009, primary completion August 2011; registered TERMINATED without a stated reason). The peer-reviewed report (Reilmann et al., Movement Disorders 2015) found AFQ056 safe and tolerable in HD but with no significant reduction in chorea versus placebo — the symptomatic anti-choreatic hypothesis failed. No subsequent HD trial, publication of continued development, or sponsor statement exists; Novartis later discontinued mavoglurant development across all indications before out-licensing to Stalicla in 2023, whose license targets substance-use and neurodevelopmental disorders. The program is recorded as discontinued, with the date anchored to the trial's primary-completion month because Novartis never announced an HD-specific discontinuation.
Development timeline
- Trial registered TERMINATED with primary completion August 2011 (month precision; no whyStopped text on the registry). The published result (Reilmann et al., Mov Disord 2015) reported no significant anti-choreatic effect versus placebo despite acceptable safety/tolerability. Discontinuation date is INFERRED from trial cessation plus the absence of any later HD activity — Novartis never issued an HD-specific discontinuation announcement; press coverage of the 2023 Stalicla deal notes Novartis had discontinued mavoglurant development across all indications.↗
- Phase 2 proof-of-concept NCT01019473 started (CT.gov month precision: November 2009): randomized, double-blind, placebo-controlled, multiple oral dose titration of AFQ056 in patients with Huntington's disease, targeting reduction of chorea.
Clinical trials in Huntington's disease
NCT01019473CAFQ056A2207Phase 2Discontinuedn=44
A Multi-centre, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multiple Oral Dose Titration Proof of Concept Study in Patients With Huntington's Disease to Reduce Chorea
missedprimaryReduction in chorea vs placebo (UHDRS-based chorea assessment) after multiple oral dose titration
AFQ056 was safe and tolerable in HD but did not significantly reduce chorea versus placebo (Reilmann R, et al. Mov Disord 2015). Numeric results paywalled; no effect size asserted.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Mavoglurant immediate-release oral capsule (twice daily) The HD proof-of-concept (NCT01019473, 2009-2011) used multiple oral dose titration of AFQ056 twice daily over 32 days of treatment (titrated up to 100 mg bid per the published report's design description). Same immediate-release oral capsule line as the contemporaneous fragile X program. | 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
- Mavoglurant (AFQ-056), GtoPdb ligand 7586 — mGlu5 negative allosteric modulator — IUPHAR/BPS Guide to PHARMACOLOGY
- NCT01019473 (CAFQ056A2207) — Phase 2 proof-of-concept of AFQ056 to reduce chorea in Huntington's disease (n=44; TERMINATED, no registry reason given) — ClinicalTrials.gov (U.S. National Library of Medicine)
- Reilmann R, et al. A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease. Mov Disord. 2015;30(3) — Movement Disorders (Wiley/MDS) / PubMed