An additional analysis of data from the CLARITY study confirmed the long-term benefits of treatment with Mavenclad (cladribine tablets) for patients with highly active relapsing forms of multiple sclerosis (MS).
The post-hoc analysis, “Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study,” was published in the Multiple Sclerosis Journal.
The safety and effectiveness of the therapy was evaluated in several Phase 2 and 3 trials and extension studies, which involved more than 2,700 relapsing MS patients, some of whom were followed for more than 10 years.
To further evaluate the effectiveness of Mavenclad, researchers reanalyzed data from the Phase 3 CLARITY trial (NCT00213135) in patients with high disease activity. They included all patients whose condition fulfilled one of two clinically relevant definitions of high disease activity, which are commonly linked to poorer treatment response.
One group included all patients who had two or more relapses during the year prior to study entry, regardless of treatment status — the high relapse activity (HRA) group. The second group included patients who had one or more relapses and evidence of disease progression (increased number of brain lesions) during the year prior to study entry while on treatment, plus patients with HRA — high relapse activity plus disease activity on treatment (HRA+DAT).
Collectively, the post-hoc analysis included 289 MS patients who participated in the CLARITY trial. Of those who met the HRA+DAT criteria, 149 received placebo during the study and 140 were treated with 3.5 mg/kg of Mavenclad.
HRA and HRA+DAT patients showed increased rates of disease activity, as demonstrated by higher relapse rates, reduced time to first relapse, and worse disability scores, as measured by the expanded disability status scale (EDSS), compared with the overall MS population of the study.
Previous results of the CLARITY trial covering all 870 MS patients who participated revealed that treatment with 3.5 mg/kg of Mavenclad reduced the risk of six-month confirmed EDSS progression by 47%, compared with placebo.
This most recent analysis showed that HRA and HRA+DAT patient subgroups were even more protected against disease progression, with an 82% reduction in the risk of six-month confirmed EDSS progression, compared with placebo.
These patients also showed a tendency toward a greater decrease in the relative risk of relapses and of new brain lesions upon treatment with Mavenclad.
Researchers also evaluated disease-free status based on NEDA, or no evidence of disease activity, scores, defined as no relapses, no three-month confirmed EDSS progression, and no new or active lesions.
Patients classified as HRA+DAT were found to be 2.2 times more likely to achieve NEDA than non-HRA+DAT patients. A similar response was found in the HRA subgroup, but the difference with the non-HRA group was not statistically significant.
“This analysis provides valuable insights on the effect of Mavenclad on patients with ongoing disease activity despite treatment with platform therapy, as well as naïve patients with more relapses at baseline, who tend to do worse over time,” Gavin Giovannoni, lead investigator in the CLARITY studies and chair of neurology at Barts and The London School of Medicine and Dentistry, said in a press release.
“The efficacy data presented in this publication show an even greater risk reduction on expanded disability status scale (EDSS) progression with Mavenclad in patients with highly active MS,” Giovannoni said.
Patients with highly active disease were not found to be more prone to adverse reactions with Mavenclad treatment, and no new safety issues were reported, compared with the overall population.
These data demonstrate that HRA and HRA+DAT patients had better, or at least comparable, clinical and MRI responses to Mavenclad as those previously reported in the overall CLARITY MS population.
Mavenclad was developed by Merck KGaA, known as EMD Serono in the U.S. and Canada, to target immune T- and B-cells that trigger relapsing MS without suppressing the entire immune system. With a maximum of 20 days of treatment over two years, the oral treatment has been shown to help patients remain relapse-free for up to four years while working to “reset” the immune system.
The therapy is already approved for use in MS in Argentina, Canada, Australia, Israel, Europe, and the United Arab Emirates, among others. EMD Serono is currently seeking its approval in the United States.
“Merck is committed to deepening our understanding of the benefit-risk profile of this innovative MS treatment in patient populations with a high need for an effective disease-modifying therapy,” said Luciano Rossetti, head of global research and development for the biopharma business of Merck.