Updated Post-Approval Safety of Cladribine Tablets in the Treatment of Multiple Sclerosis, With Particular Reference to Respiratory Viral Infections and COVID-19

Background: Several integrated analyses have reported on the safety of cladribine tablets 10 mg (3 5 mg/kg cumulative dose over 2 years [CT3 5]) during clinical development for the treatment of patients with relapsing multiple sclerosis (RMS) Additional real-life safety data have accrued since the approval of CT3 5 in many countries worldwide In recent months the COVID-19 pandemic has become a concern for MS patients and their healthcare providers in terms of the associated safety of their disease-modifying therapy Objectives: To update on the post-approval safety profile of CT3 5 in patients with RMS, including COVID-19 and other respiratory viral infections Methods: Serious and non-serious adverse events (AEs) from post-approval sources (including spontaneous individual case safety reports, non-interventional post-marketing studies, and reports from other solicited sources) are presented to Jan 2020 AE rates are shown as crude incidences (events/number of patients) Up-to-date COVID-19 findings are summarized Results: A total of 2570 AEs were reported for the first 14,813 patients who received CT3 5 post-approval;303 (12%) events were classified as serious and none represented a new safety signal Crude incidences for AEs of special interest were as follows: severe lymphopenia, 0 002;herpes zoster, 0 008;tuberculosis, 0 0004;severe infections, 0 009;progressive multifocal leukoencephalopathy, 0;opportunistic infections, 0 001;malignancies, 0 0015;and teratogenicity, 0 The majority of opportunistic infections were superficial dermal and mucosal fungal infections that resolved on standard treatments The pattern of respiratory viral infections (typically non-serious) with post-approval use of CT3 5 was also consistent with that from the clinical development program;crude incidences were as follows: influenza, 0 005;viral infection, 0 002;and viral upper respiratory tract infection, 0 0004 As of 29 Jun 2020, the Merck safety database included 18 cases of confirmed COVID-19 in CT3 5-treated patients An update on latest findings on COVID-19 infections will be presented, including analysis of time of infection since treatment where available Conclusions: No new safety signals were identified in the realworld post-approval data of CT3 5, cumulative to Jan 2020 The safety profile of CT3 5, including respiratory viral infections, is consistent with previously published integrated safety analyses of the clinical development data