An analysis of data from the phase 3 development of cladribine (Mavenclad; EMD Serono) showed that the incidence of treatment-emergent adverse events was low and most were mild in intensity.
Jiwon Oh, MD, PhD
A new post-hoc analysis of pooled data from the phase 3 development of cladribine (Mavenclad; EMD Serono) showed that the incidence of treatment-emergent adverse events (AEs) was low and mostly mild, indicating that the tablets are generally well tolerated and could influence better adherence for patients with multiple sclerosis (MS).1
All told, nausea, headache, and lymphopenia were seen more frequently in patients treated with cladribine tablets than placebo patients in the CLARITY (NCT00213135) and ORACLE-MS (NCT00725985) clinical trials. Within the first 2 to 12 weeks of treatment, the incidence of AEs ranged from 68.0% to 54.4% for those on cladribine, compared with 68.4% to 53.8% for those on placebo.
The findings were presented by Jiwon Oh, MD, PhD, assistant professor of medicine, Division of Neurology, University of Toronto, and scientist, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, and colleagues at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting.
“Tolerability and adherence to disease-modifying drugs can be influenced by treatment-emergent AEs that start soon after therapy initiation. One potential advantage of cladribine tablets is that patients only receive doses for two 4- to 5-day periods per treatment year,” Oh and colleagues wrote.
This analysis of the safety populations in CLARITY and ORACLE-MS studies included patients with MS who received cladribine tablets in a 3.5 mg/kg cumulative dose over 2 years (n = 636) or placebo (n = 641). The incidence of early AEs, treatment-emergent AEs, serious treatment-emergent AEs, drug-related treatment-emergent AEs, and treatment-emergent AEs leading to discontinuation were summarized based on their incidence within 2, 6, and 12 weeks post-initiation of treatment.
When breaking the data down by time epoch after initiation, the most common treatment-emergent AEs at the 2-week mark were nausea (placebo: 3.3%; cladribine: 4.9%), fatigue (placebo: 2.0%; cladribine: 1.4%), and headache (placebo: 8.3%; cladribine: 9.0%); and at the 6-week mark were nausea (placebo: 3.7%; cladribine: 6.4%), fatigue (placebo: 3.1%; cladribine: 2.5%), headache (placebo: 11.9%; cladribine: 14.8%), and lymphopenia (placebo: 0%; cladribine: 2.5%).
At the 12-week mark, the most common treatment-emergent AEs were nausea (placebo: 4.5%; cladribine: 8.0%), fatigue (placebo: 4.4%; cladribine: 3.1%), headache (placebo: 15.1%; cladribine: 18.4%), lymphopenia (placebo: 0.5%; cladribine: 6.8%), and leukopenia (placebo: 0%; cladribine: 1.3%).
Cladribine was approved by the FDA for the treatment of relapsing MS, as well as active secondary progressive MS, in March 2019. The treatment was not, however, recommended for use among patients with clinically isolated syndrome. The purine analog is a synthetic agent that targets lymphocytes and selectively suppresses the immune system, with the goal of depleting lymphocytes in order to “reset” it. It was approved based on the data from a trial including more than 1300 patients with relapsing forms of MS, ultimately showing a significant decrease in the number of relapses experienced by patients who had ≥1 relapse in the previous year, compared to placebo.2
Earlier this year, at the 2020 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum, another post hoc analysis of CLARITY suggested that regardless of baseline Expanded Disability Status Scale (EDSS) scores, treatment with cladribine tablets effectively reduced the risks of progressing to secondary progressive MS in patients with relapsing disease, within 2 years of treatment. That data showed overall proxy SPMS progression in just 6.7% of cladribine 3.5 mg/kg patients (n = 433), compared with 13.5% for placebo (n = 437; odds ratio [OR] 0.46 [95% CI, 0.28—0.76]; P = .0024).3
Additionally, while on-site at ACTRIMS 2020, NeurologyLive spoke with Augusto Miravalle, MD, associate professor, department of neurology, University of Colorado, and neurologist, Advanced Neurology of Colorado, to discuss the ongoing CLICK-MS study (NCT03933215), which he and colleagues launched in May 2019. It is examining the real-world effectiveness and safety of the cladribine, as well as patient-reported outcomes. More specifically, it is assessing these changes in patients with relapsing MS who transition to cladribine after suboptimal response to injectable disease-modifying therapies.
Watch Miravalle offer his insight on the advantages of the EMD Serono agent below.
For more coverage of CMSC 2020, click here.
1. Oh J, Walker B, Giovannoni G, et al. Treatment-Emergent Adverse Events Occurring Early in the Treatment Course of Cladribine Tablets in Two Phase 3 Trials in Multiple Sclerosis. Int J MS Care. 2020;22(2 Suppl). DMT04.
2. FDA approves new oral treatment for multiple sclerosis [press release]. Silver Spring, MD: FDA; Published March 29, 2019. Accessed May 28, 2020. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634837.htm.
3. Vermersch P, Giovannoni G, Soelberg-Sorensen P, et al. Reduction of risk of secondary progressive multiple sclerosis within 2 years of treatment with cladribine tablets: an analysis of the CLARITY study. Presented at 2020 ACTRIMS forum. February 27-29, 2020; West Palm Beach, Florida. Abstract P113.