AFQ056 · program
Mavoglurant for Obsessive-compulsive disorder
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) as augmentation therapy in obsessive-compulsive disorder resistant to SSRI treatment (NCT01813019, CAFQ056A2225): randomized, double-blind, placebo-controlled, parallel-group, in patients who had failed an adequate SSRI course (12+ weeks at appropriate doses). Started November 2013, the study was prematurely terminated at the time of the first interim analysis (November 2014, n=50 of a planned ~60 randomized) because it did not meet its primary efficacy objective. The published report (Rutrick et al., Advances in Therapy 2017) confirmed that mavoglurant augmentation did not demonstrate efficacy over placebo in SSRI-resistant OCD. No further development in OCD by Novartis or by Stalicla (whose 2023 worldwide license is directed at substance-use and neurodevelopmental disorders); the program is discontinued.
Development timeline
- Registry whyStopped: 'Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective.' CT.gov completion month November 2014 (month precision; day is an anchor). The 2017 publication confirmed lack of efficacy over placebo, and no sponsor has developed mavoglurant in OCD since.
- Phase 2 proof-of-concept NCT01813019 started (CT.gov month precision: November 2013): AFQ056 vs placebo augmentation in OCD patients resistant to SSRI treatment.
Clinical trials in Obsessive-compulsive disorder
NCT01813019CAFQ056A2225Phase 2Discontinuedn=50
A Randomized, Double-blind, Placebo-controlled, Parallel-group Proof of Concept Study to Evaluate the Effect of AFQ056 in Obsessive Compulsive Disorder (OCD) Patients Resistant to SSRI Treatment
missedprimaryPrimary efficacy objective (obsessive-compulsive symptom reduction vs placebo as SSRI augmentation)
Terminated at the first interim analysis for failure to meet the primary efficacy objective; the published report (Rutrick et al., Adv Ther 2017) confirmed mavoglurant augmentation did not demonstrate efficacy over placebo in SSRI-resistant OCD. Numeric results are paywalled; no effect size asserted.
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
- 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)
- Rutrick D, et al. Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study. Adv Ther. 2017;34(2) — Advances in Therapy (Springer) / PubMed