A phase 2 open-label clinical trial to determine the effect of famciclovir on Epstein-Barr virus activity as measured by EBV shedding in the saliva of people with multiple sclerosis

Background There is increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS. No treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS ([NCT05283551][1]). Methods People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting Famciclovir 500mg bd. 12 saliva samples were provided on treatment and 12 following treatment. A real-time quantitative PCR Taqman assay targeted to a non-repeated sequence of the EBV polymerase gene was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test. Results 30 patients were recruited (19F; mean age 41 years; median EDSS 3.5). 29 patients received famciclovir, 24 completed the 12-week course. 21 participants provided at least one usable saliva sample in all 3 epochs. 10/21 participants had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events. Conclusions No significant effect of famciclovir on EBV shedding was seen. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies; this requires replication. Anonymised participant-level data is available from the authors on request [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05283551&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F20%2F2023.08.18.23294265.atom