Safety and efficacy of cladribine, glatiramer acetate, and more

Interim data on long-term efficacy and durability of effect of cladribine tablets from CLASSIC-MS, with a median of 10 years follow-up, were presented [1]. Interim results of 147 participants of this phase 4 study suggested sustained efficacy of cladribine following 2 annual treatment cycles, with a substantial proportion of patients requiring no further treatment with a disease-modifying treatment or assistive ambulatory device. Median time since last parent study dose (LPSD) was 10 (range 8-14) years. Of 147 patients, 139 (94.6%) did not use a wheelchair/were not bedridden in the 3 months prior to CLASSIC-MS; 123 (83.7%) did not need an ambulatory device (EDSS <6) at any time since LPSD. The majority of patients (93/147: 63.3%) received no subsequent DMT after LPSD, and 59.1% maintained active employment.

The safety, tolerability, and efficacy in terms of NEDA-3 of glatiramer acetate long-acting injection in the subpopulation of 10 relapsing-remitting MS patients who completed the core study and finished 3 years of the study extension were encouraging [2]. Mean EDSS score after 4 years showed no change versus baseline. There were no relapses or MRI activity. NEDA-3 over 4 years was achieved by 90% of the per protocol population. The number of adverse events was significantly reduced during the extension study. No unexpected adverse events were reported. According to the authors, these results further support the assumption of the potential of glatiramer acetate long-acting injection to improve MS treatment by significantly reducing the frequency of injections, increasing adherence, and providing a therapeutic benefit.

Effects of ponesimod on prespecified MRI-based endpoints and NEDA status in relapsing MS patients in the phase 3 OPTIMUM study were evaluated [3]. Patients were randomised to ponesimod or teriflunomide for 108 weeks. Of 1,133 participants, 985 (86.9%) completed the study. For all MRI outcomes, including whole brain volume loss, ponesimod showed more benefit than teriflunomide. A significantly higher percentage of patients treated with ponesimod achieved NEDA-3 and NEDA-4 status. At week 108, 28.2% and 18.3% of patients in the ponesimod and teriflunomide groups, respectively, achieved NEDA-3 (OR 1.70; P=0.0004); 15.0% and 8.5% achieved NEDA-4 (OR 1.85; P=0.0026).

The clinical effectiveness of natalizumab, fingolimod, and BRACETD (interferon-β, glatiramer acetate, dimethyl fumarate, or teriflunomide) was compared in patients with rapidly evolving severe relapsing-remitting MS in a real-world setting [4]. Mean follow-up was approximately 3 years. Annualised relapse rate was lowest with natalizumab, followed by fingolimod and BRACETD (ARR 0.18 vs 0.29 vs 0.39, respectively; P<0.001 for all comparisons). Risk of first relapse was lower with natalizumab versus fingolimod or BRACETD (HR 0.63 and 0.41; P<0.001 for both) and with fingolimod versus BRACETD (HR 0.66; P<0.001). Confirmed disability improvement was more likely with natalizumab than with fingolimod (HR 1.25; P=0.047) or BRACETD (HR 1.46; P=0.002).

1. Giovannoni G, et al. CLASSIC-MS: Long-term efficacy and real-world treatment patterns for patients receiving cladribine tablets - interim data with 8–14 years follow-up. MSVirtual 2020, Abstract LB1229.
2. Fletcher S, et al. Glatiramer Acetate Depot (Extended-Release) Phase IIa Study in Patients with RRMS: Safety, Tolerability and Efficacy Four-Years Analysis. MSVirtual 2020, Abstract LB1228.
3. Kappos L, et al. Effect of oral ponesimod on clinical disease activity and MRI-based outcomes in patients with relapsing multiple sclerosis: Phase 3 OPTIMUM study. MSVirtual 2020, Abstract P0071.
4. Spelman T, et al. Comparative effectiveness of natalizumab, fingolimod, and first-line therapies for rapidly evolving severe relapsing-remitting multiple sclerosis. MSVirtual 2020, Abstract P0859.

 



Posted on 25 November, 202025 March, 2024