Mavenclad Effectively Lowers Relapse Rates, Study Comparing DMTs Finds

Mavenclad (cladribine) appears to be better at lowering relapse rates during the first two years of disease in relapsing-remitting multiple sclerosis (RRMS) patients than other MS therapies, including interferon, Copaxone (glatiramer acetate) and Tecfidera (dimethyl fumarate), a head-to-head observational study found.

Mavenclad, however, was less effective at reducing these rates than Tysabri (natalizumab).

The study “Cladribine vs other drugs in MS,” comparing data from Mavenclad’s pivotal trial with data collected on patients across Italy on a first disease-modifying therapy, was published in the journal Neurology.

Mavenclad, developed and marketed by EMD Serono (known as Merck KGaA outside North America), is an oral, short-course therapy approved for relapsing forms of MS in more than 50 countries, including in the U.S., European Union, Australia, and Canada.

The therapy, given in two treatment courses of two weeks each, separated by about one year, works by lowering the number of immune cells in the bloodstream, the cause of neurodegeneration in MS.

Mavenclad’s approval was supported by findings from a clinical trial program involving a total of 1,976 MS patients, including the Phase 3 CLARITY trial (NCT00213135).

In the CLARITY study, 1,326 RRMS patients were randomized to a placebo or to one of two doses of Mavenclad, 3.5 and 5.25 mg/kg. The approved dose is 3.5 mg/kg.

Results showed that both doses were superior to placebo in suppressing relapses, and in increasing the time patients remained relapse-free. Treatment with 3.5 mg/kg of Mavenclad reduced the risk of six-month disability progression by 47%, compared with placebo, as measured by the expanded disability status scale (EDSS).

However, few studies have compared Mavenclad’s effectiveness with other approved RRMS therapies.

“We aim to fill in the gap in the current RRMS treatment landscape, as no direct head-to-head comparisons of cladribine with other common immunotherapies have yet been conducted,” the scientists wrote.

Researchers at the University of Genoa and colleagues performed a retrospective comparative analysis of data from the CLARITY study and the i-MuST study, a retrospective database involving 24 Italian MS centers.

The i-MuST database included 3,150 patients, diagnosed between 2010 and 2018, who began treatment with disease-modifying therapies (DMTs) and who satisfied the inclusion criteria for the CLARITY study.

In total, they analyzed data covering 2,204 patients from i-MuST and 945 patients from CLARITY. Patients in i-MUST tended to be younger than those in CLARITY, but their EDSS levels were “generally well balanced,” the study noted.

Data from i-MuST covered 1,168 patients being treated with an interferon (including IFN-1a, IFN beta-1a, and IFN beta-1b, all sold under several brand names), 402 with Copaxone, 295 with Tecfidera, 149 with Tysabri, 113 with Gilenya (fingolimod), and 77 with Aubagio (teriflunomide).

In the CLARITY data set, 640 patients were randomized to Mavenclad — 322 at the 3.5 mg/kg, and 318 the 5.25 mg/kg dose — and 305 were given a placebo.

For treatment comparisons, the interferon groups and the two Mavenclad groups were analyzed as single groups.

The analysis’ primary aim was to compare the effectiveness of these treatments in reducing the annualized relapse rate (ARR) over two years. Additional (secondary) aims included the time to onset of 24-week confirmed disability progression over two years.

Results showed that treatment with Mavenclad led to a statistically significant reduction in ARR vs. interferon (reduction of 52%), vs. Copaxone (by 51%), and vs. Tecfidera (by 40%). No significant difference  in annual relapse rates was seen compared with Gilenya.

Tysabri was significantly better at lowering ARR than Mavenclad, with patients treated with Mavenclad showing a two times higher ARR ratio. No comparison was possible between Mavenclad and Aubagio due to the low number of treated patients in the Aubagio group.

All DMTs analyzed were better than the placebo, in agreement with results from clinical trials.

Researchers also assessed the effectiveness of Mavenclad tablets against other DMTs according to a person’s baseline disease activity.

Mavenclad was found to be significantly better for patients with high disease activity (HDA) compared to all other DMTs, except for Gilenya and Tysabri. This was true for both doses of Mavenclad.

“With our comparative results, based on a wide national database (i-MuST) and the CLARITY data set, we simulated a scenario representing the complexity of management of patients with MS, which confirms the effectiveness of cladribine tablets in treating RRMS,” the researchers wrote.

Overall, “cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate [Copaxone], or dimethyl fumarate [Tecfidera]; was similar to fingolimod [Gilenya]; and was higher than natalizumab [Tysabri],” they concluded.

The researchers also noted that the benefits of Mavenclad treatment “was generally amplified in the subgroup of patients with high disease activity.”

This study was sponsored by Merck Serono S.p.A., a Rome-based affiliate of Merck KGaA.