Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach

Vivien Li; Fiona C McKay; David C Tscharke; Corey Smith; Rajiv Khanna; Jeannette Lechner-Scott; William D Rawlinson; Andrew R Lloyd; Bruce V Taylor; Julia M Morahan; Lawrence Steinman; Gavin Giovannoni; Amit Bar-Or; Michael Levy; Natalia Drosu; Andrew Potter; Nigel Caswell; Lynne Smith; Erin C Brady; Bruce Frost; Suzanne Hodgkinson; Todd A Hardy; Simon A Broadley; Australian Anti-EBV Drugs for MS Working Group

doi:10.1007/s40263-024-01153-5

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach

CNS Drugs. 2025 Jan 10. doi: 10.1007/s40263-024-01153-5. Online ahead of print.

Authors

Vivien Li¹, Fiona C McKay², David C Tscharke³, Corey Smith⁴, Rajiv Khanna⁴, Jeannette Lechner-Scott^{5

6}, William D Rawlinson⁷, Andrew R Lloyd⁸, Bruce V Taylor⁹, Julia M Morahan¹⁰, Lawrence Steinman¹¹, Gavin Giovannoni¹², Amit Bar-Or¹³, Michael Levy¹⁴, Natalia Drosu¹⁴, Andrew Potter¹⁰, Nigel Caswell¹⁵, Lynne Smith¹⁵, Erin C Brady¹⁵, Bruce Frost¹⁵, Suzanne Hodgkinson¹⁶, Todd A Hardy¹⁷, Simon A Broadley^{18

19}; Australian Anti-EBV Drugs for MS Working Group

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3010, Australia.
² Multiple Sclerosis Australia, Suite 3.01 18 Flour Mill Way, Summer Hill, NSW, 2130, Australia. fiona.mckay@msaustralia.org.au.
³ Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
⁴ Immunology Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
⁵ University of Newcastle, School of Medicine and Public Health, Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia.
⁶ Department of Neurology, John Hunter Hospital, New Lambton Heights, NSW, 2305, Australia.
⁷ Serology and Virology Division (SAViD), Microbiology NSW Health Pathology, Randwick, NSW, 2031, Australia.
⁸ The Kirby Institute, University of New South Wales, Kensington, NSW, 2052, Australia.
⁹ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
¹⁰ Multiple Sclerosis Australia, Suite 3.01 18 Flour Mill Way, Summer Hill, NSW, 2130, Australia.
¹¹ Departments of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 9305-5101, USA.
¹² Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Queen Mary University of London, London, E1 2AT, UK.
¹³ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁴ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
¹⁵ National Advocates, Multiple Sclerosis Australia, Summer Hill, NSW, 2130, Australia.
¹⁶ School of Clinical Medicine, University of New South Wales, Liverpool, NSW, 2170, Australia.
¹⁷ Department of Neurology, Concord Hospital, University of Sydney, Concord West, NSW, 2039, Australia.
¹⁸ School of Medicine and Dentistry, Gold Coast Campus, Griffith University, Southport, QLD, 4222, Australia.
¹⁹ Department of Neurology, Gold Coast University Hospital, Southport, QLD, 4215, Australia.

PMID: 39792343
DOI: 10.1007/s40263-024-01153-5

Abstract

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Methods: A list of therapies with anti-EBV effects was developed from existing reviews. A detailed review of pre-clinical and clinical data was undertaken to assess these candidates for potential usefulness and possible harm in MS. A 'drug-CV' and a plain language version focusing on tolerability aspects was created for each candidate. We used validated criteria to score each candidate with an international scientific panel and people living with MS.

Results: A preliminary list of 11 drug candidates was generated. Following review by the scientific and lived experience expert panels, six yielded the same highest score. A further review by the expert panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) deemed to have the best balance of efficacy, safety and tolerability for use in MS.

Conclusions: Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS.