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N03 Efficacy, Safety, And Tolerability Of Afq056 For The Treatment Of Chorea In Patients With Huntington’s Disease
  1. R Reilmann1,2,
  2. M Rouzade-Dominguez3,
  3. C Saft4,
  4. SD Süssmuth5,
  5. J Priller6,
  6. A Rosser7,
  7. H Rickards8,
  8. L Schöls9,
  9. N Pezous10,
  10. F Gasparini11,
  11. GB Landwehrmeyer5,
  12. D Johns12,
  13. B Gomez-Mancilla11
  1. 1George-Huntington-Institute, Technology-Park, Deilmann-Building IV, Johann-Krane-Weg 27, 48149 Münster
  2. 2Department of Neurology, University of Münster, Albert Schweitzer Campus 1 – Building A1, 48149 Münster, Germany
  3. 3Clinical Sciences and Innovation, Novartis Pharma AG, CH-4056, Basel, Switzerland
  4. 4Neurologische Klinik Der Ruhr-Universität Bochum St Joseph, Hospital Gudrunstrasse 56, 44791 Bochum, Germany
  5. 5Department of Neurology, Ulm University, Oberer Eselsberg 45/1, 89081 Ulm, Germany
  6. 6Department of Neuropsychiatry, Charité-Uni Versitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
  7. 7Cardiff University Schools of Medicine and Biosciences, Neuroscience and Mental Health Research Institute, Life Sciences Building, Museum Avenue, Cardiff, CF10 3AX, UK
  8. 8Department of Neuropsychiatry, The Barberry, 25 Vincent Drive, Edgbaston, Birmingham, B15 2FG, UK
  9. 9Clinical Neurogenetics Unit,Center of Neurology and Hertie Institute for Clinical Brain Research, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany
  10. 10IIS Translational Sciences – Early Development Statistical Research, Novartis Pharma AG, CH-4002, Basel, Switzerland
  11. 11Novartis Institutes for Biomedical Research, Novartis Pharma AG, CH-4056, Basel, Switzerland
  12. 12Neuroscience Translational Medicine,Novartis Institutes for Biomedical Research Inc., 220 Massachusetts Avenue 330H, Cambridge, MA 02139, USA


Background Treatments of chorea in patients with HD have limited efficacy and side-effects. AFQ056, a selective metabotropic glutamate receptor-5 antagonist shown to reduce levodopa-induced dyskinesia in PD, was hypothesised to reduce chorea in HD.

Objective To assess anti-choreatic efficacy, safety, and tolerability of AFQ056 (Mavoglurant) in HD.

Methods This was a 32-day randomised, double-blind, parallel-group, placebo (pbo)-controlled, proof-of-concept study. Patients were 30–85 years old, with HD (CAG ≥36) in clinical stage I–III, and maximal chorea sum score >10 in the UHDRS-TMS. Patients were randomised (1:1) to AFQ056 (Days 1–12, titration 25–150mg bid; Days 13–28, 150mg bid; Days 29–32, 50mg bid) or pbo. Primary objectives were to assess efficacy of AFQ056 vs pbo at Day 28 on UHDRS-TMS maximal chorea sum score and orientation index (non-dominant hand) from quantitative-motor (Q-Motor) grasping task and to assess safety and tolerability of AFQ056. Key secondary efficacy assessments included total UHDRS-TMS, UHDRS-TMS Luria score, UHDRS-TMS finger taps, and additional Q-Motor measures.

Results Overall 42 patients (mean age 55.2 years, HD duration 6.6 years) were randomised. At Day 28, there were no significant improvements on UHDRS-TMS maximal chorea sum score (p = 0.155) or orientation index (non-dominant hand, p = 0.626) in AFQ056-treated patients vs pbo. A significant reduction in Q-Motor speeded-tapping variability was observed favouring AFQ056 vs pbo (p = 0.011) and reverting at study end; this was accompanied by UHDRS-TMS finger-tapping scores showing a trend towards improvement. No significant treatment effects were observed at Day 28 on other key secondary endpoints. Adverse events were reported by 14 and 12 AFQ056- and pbo-treated patients, respectively.

Conclusions AFQ056 did not reduce involuntary choreatic movements in HD. The Q-Motor findings in speeded-tapping may reflect an improvement in fine motor coordination, but their clinical relevance is unknown. Overall, AFQ056 was well tolerated.

Study supported by Novartis Pharma AG.

  • clinical trial
  • chorea

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