Mavoglurant Explained

Mavoglurant (developmental code name AFQ-056) is an experimental drug candidate for the treatment of fragile X syndrome and other conditions.[1] [2] It exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGluR5).[3] [4] [5]

Mavoglurant was under development by Novartis and reached phase II and phase III clinical trials.[2] [6] Phase IIb/III dose finding and evaluation trials for fragile X-syndrome were discontinued by the end of 2014.[7] Otherwise, it would have been the first drug to treat the underlying disorder instead of the symptoms of fragile X syndrome.[8] Mavoglurant was also in phase II clinical trials for Levodopa-induced dyskinesia.[9] [10] In 2007, Norvartis had conducted a clinical study to assess its ability of reducing cigarette smoking, but no results had been published up till now. Novartis was conducting a clinical trial with this drug on obsessive–compulsive disorder.

Novartis discontinued development of mavoglurant for fragile X syndrome in April 2014 following disappointing trial results. Development was discontinued for other indications by 2017.

Recently, Stalicla, a biotech company applying artificial intelligence to identify subgroups of high-responder patients, acquired worldwide rights from Novartis to progress the drug for substance-use and neurodevelopmental disorders.[11] [12] [13]

See also

Notes and References

  1. Web site: Mavoglurant . AdisInsight . Springer Nature Switzerland AG .
  2. Cole P . Mavoglurant . Drugs of the Future . 2012 . 37 . 1 . 7–12 . 10.1358/dof.2012.037.01.1772147. 258330291 .
  3. Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, Song C, Buijsen RA, Pop AS, Gomezmancilla B, Nelson DL, Willemsen R, Gasparini F, Oostra BA . 6 . AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome . Neurobiology of Disease . 42 . 3 . 311–317 . June 2011 . 21316452 . 10.1016/j.nbd.2011.01.022 . 45389434 .
  4. Arsova A, Møller TC, Vedel L, Hansen JL, Foster SR, Gregory KJ, Bräuner-Osborne H . Detailed In Vitro Pharmacological Characterization of Clinically Tested Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5 . Molecular Pharmacology . 98 . 1 . 49–60 . July 2020 . 32358164 . 7705108 . 10.1124/mol.119.119032 .
  5. Witkin JM, Pandey KP, Smith JL . Clinical investigations of compounds targeting metabotropic glutamate receptors . Pharmacology, Biochemistry, and Behavior . 219 . 173446 . September 2022 . 35987339 . 10.1016/j.pbb.2022.173446 . 251600367 .
  6. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, Cornish K, He Y, Paulding C, Neri G, Chen F, Hadjikhani N, Martinet D, Meyer J, Beckmann JS, Delange K, Brun A, Bussy G, Gasparini F, Hilse T, Floesser A, Branson J, Bilbe G, Johns D, Gomez-Mancilla B . 6 . Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056 . Science Translational Medicine . 3 . 64 . 64ra1 . January 2011 . 21209411 . 10.1126/scitranslmed.3001708 . 206677267 .
  7. Web site: Novartis Discontinues Development of mavoglurant (AFQ056) for Fragile X Syndrome . Fragile X Research . FRAXA Research Foundation. 2014-04-24.
  8. Web site: AFQ056 drug improves symptoms in Fragile X patients: Study . news-medical.net . January 9, 2011 .
  9. Kumar R, Hauser RA, Mostillo J, Dronamraju N, Graf A, Merschhemke M, Kenney C . Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients . The International Journal of Neuroscience . 126 . 1 . 20–24 . Sep 2013 . 24007304 . 10.3109/00207454.2013.841685 . 7531940 .
  10. Web site: AFQ056 & Parkinson Search . ClincalTrials.gov . U.S. National Library of Medicine .
  11. Web site: LaHucik K . Novartis offloads neurodevelopmental disorder asset to small Swiss biotech. 2023-01-09 . Endpoints News .
  12. Web site: Stalicla Inks Mavoglurant Deal With Novartis. 2023-01-12 . Inside Precision Medicine; Genetic Engineering & Biotechnology News. . Mary Ann Liebert .
  13. Web site: STALICLA attracts US partner for Phase 3 development of anti-cocaine drug. 2023-03-13 . Startupticker Foundation .

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