Cladribine Shows Long-Term Efficacy in Delaying MS Conversion, Favorable Efficacy Compared With Other Oral DMTs

Gavin Giovannoni, MBBCh, PhD

Data from the phase 4 CLASSIC-MS study (NCT03961204) suggest that patients who experienced a first clinical demyelinating event and were treated with cladribine (Mavenclad; EMD Serono) over a median 9.5 years of follow-up since last dose experienced long-term sustained efficacy, delayed conversion to clinically definite multiple sclerosis (MS), and fewer second relapses compared with nontreated patients.¹

Since first dose in the respective parent study, 50% (n = 78) of patients exposed to cladribine experienced conversion to clinically definite MS compared with 77.5% (n = 55) of the unexposed group, with median time to conversion for the groups of 3.36 years (range, 0.0-11.1) and 1.21 years (range, 0.0-10.7), respectively. In the cladribine-exposed group, 53.2% of patients remained relapse-free since their last parent study dose compared with 28.2% of the unexposed cohort.

The data were presented by Gavin Giovannoni, MBBCh, PhD, chair of neurology, Blizzard Institute, Barts and The London School of Medicine and Dentistry, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, held February 24-26, in West Palm Beach, Florida.

The proportion of patients not using a wheelchair in the 3 months preceding CLASSIC-MS or not bedridden since last parent study dose—defined as EDSS score less than 7—was 98.7% of the cladribine-exposed cohort compared with 94.2% of the unexposed group. The proportions of those not requiring an assistive ambulatory device at any time since last parent study dose—defined as EDSS score less than 6—were 97.4% and 94.4%, respectively. Of those exposed, 84.6% (n = 132) were actively employed at inclusion in CLASSIC-MS compared with 77.5% (n = 55) of never exposed patients.

The exploratory and ambispective CLASSIC-MS study was a follow-up of those individuals who were originally enrolled in a parent study—one of the phase 3 studies of cladribine: CLARITY (NCT00213135) and its extension study (NCT00641537), and ORACLE MS (NCT00725985). This analysis included 227 patients who were included in CLASSIC-MS after participating in ORACLE MS, having received at least one course of cladribine tablets (68.7%) or placebo (31.3%). That cohort accounted for 34.3% of the total CLASSIC-MS population.

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Of those 227 individuals, 65.5% of them were women, with a mean cohort age of 42.7 years and a mean Expanded Disability Status Scale (EDSS) score of 2.15 at baseline of CLASSIC-MS. The median time since last parent study dose was 9.5 years (range, 8.2-11.2). A total of 68.7% (n = 156) of the cohort were exposed to cladribine during ORACLE MS and 31.3% (n = 71) were never exposed during ORACLE MS.

Additional data from the Generating Learnings In Multiple Sclerosis (GLIMPSE) study, a longitudinal, retrospective analysis of adult patients identified with RMS, were also presented at ACTRIMS Forum 2022 by Helmut Butzkueven, MBBS, FRACP, PhD, Department of Neuroscience, Central Clinical School, Monash University, Melbourne. GLIMPSE included 633 patients on cladribine from the MSBase Registry who were propensity score matched with those receiving fingolimod (Gilenya; Novartis)(n = 1195), dimethyl fumarate (Tecfidera; Biogen)(n = 912) or teriflunomide (Aubagio; Biogen)(n = 735). The median follow-up times were between 11-13 months.²

“It is important in a lifelong disease like MS to continue assessing the efficacy and safety of available treatment options in the real world,” Butzkueven said in a statement.³ “This is where the MSBase Registry, using standardized data records from over 79,000 people with MS around the world, can provide information that is not possible to obtain in a randomized clinical trial. This information showed us that in GLIMPSE, MAVENCLAD had better relapse outcomes and longer treatment persistence compared to other oral DMTs, including fingolimod.”

In the cladribine vs fingolimod analysis (n = 520 per group), the annualized relapse rates (ARRs) were 0.09 and 0.15, respectively (P = .02). The HR for time-to-first relapse as 0.60 (95% CI, 0.41-0.88; P = .01) and for time-to-discontinuation was 0.22 (95% CI, 0.14-0.34; P <.001). In the cladribine vs dimethyl fumarate analysis (n = 450 per group), the ARRs were 0.10 and 0.15, respectively (P = .03). The HR for time-to-first relapse was 0.58 (95% CI, 0.37-0.90; P = .02) and HR for time-to-discontinuation was 0.10 (95% CI, 0.06-0.17; P <.001). In the cladribine vs teriflunomide analysis (n = 458 per group), the ARRs were 0.09 and 0.17, respectively (P <.001). The HR for time-to-first relapse was 0.33 (95% CI, 0.21-0.52; P <.001) and for time-to-discontinuation was 0.10 (95% CI, 0.06-0.17; P <.001).

The between-group differences equated to a 40%, 42%, and 67% lower time-to-first relapse in cladribine-treated patients compared with those treated with fingolimod, dimethyl fumarate, and teriflunomide, respectively. The time to switch rate in patients treated with cladribine was 4.0, 7.0, and 6.5 times lower than fingolimod, dimethyl fumarate, and teriflunomide, respectively.

For more coverage of ACTRIMS Forum 2022, click here.

REFERENCES
1. Leist T, Giovanonni G, Aydemir A, et al. Primary Results from 8-11 Years of Follow-up in the CLASSIC-MS Study Show Long-term Efficacy for Patients Who Received Cladribine Tablets in ORACLE MS. Presented at ACTRIMS Forum; February 24-26, 2022; West Palm Beach, Florida. P107.
2. Butzkueven H, Spelman T, Ozakbas S, et al. Real-World Comparative Effectiveness and Persistence of Cladribine Tablets and Other Oral Disease-Modifying Treatments for Multiple Sclerosis from GLIMPSE: Results from the MSBase Registry. Presented at ACTRIMS Forum; February 24-26, 2022; West Palm Beach, Florida. P342.
3. New MAVENCLAD® Data at ACTRIMS Forum 2022 Show Favorable Efficacy Outcomes Versus Other Oral DMTs and Lower Occurrence of Further Relapses or Disability Progression. News release. EMD Serono. February 24, 2022. Accessed February 25, 2022. https://www.biospace.com/article/releases/new-mavenclad-data-at-actrims-forum-2022-show-favorable-efficacy-outcomes-versus-other-oral-dmts-and-lower-occurrence-of-further-relapses-or-disability-progression/