Several integrated analyses have reported on the safety of cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years [CladT3.5]) during clinical development for treatment of relapsing multiple sclerosis (MS). Additional real-life safety data have accrued since the approval of CladT3.5 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.
To update on the post-approval safety profile of CladT3.5 in patients with relapsing MS, including COVID-19 and other respiratory viral infections.
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 July 2020. AE rates are shown as crude incidences.
3357 AEs were spontaneously reported for the first 18,463 patients who received CladT3.5 post-approval; 435 (13%) of these events were serious. Crude incidences for AEs of special interest: severe lymphopenia, 0.21%; herpes zoster, 1.07%; tuberculosis, 0.05%; severe infections, 1.23%; progressive multifocal leukoencephalopathy, 0%; opportunistic infections, 0.04%; malignancies, 0.23%; and congenital anomalies, 0%. The pattern of respiratory viral infections (typically non-serious) with post-approval use of CladT3.5 was also consistent with that of the clinical development program; crude incidences: H1N1 influenza, 0.01%; influenza, 0.68%; viral infection, 0.27%; and viral upper respiratory tract infection, 0.04%. As of 7 September 2020, the Merck KGaA safety database included 85 cases of suspected COVID-19 in CladT3.5-treated patients (confirmed by test, n=38). An update on latest findings on COVID-19 infections will be presented, including analysis of time of infection since treatment where available.
The safety profile of CladT3.5, including respiratory viral infections, is consistent with previously published integrated safety analyses of the clinical development data.