More than half who received it in clinical trials didn’t need further DMTs
by Steve Bryson, PhD |
More than half of those who received the oral therapy in the clinical trials that supported its approval no longer needed further disease-modifying therapies (DMTs) and twice as many continued relapse-free over a median of 10.9 years compared with those never given it.
The real-world study, “Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS: An ambispective study,” was published in the Multiple Sclerosis Journal.
Mavenclad, marketed by EMD Serono, is a short-course oral DMT approved for relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS). It works by lowering the number of immune cells circulating in the bloodstream that drive inflammation and nerve damage in MS.
Its approval was supported by data from three Phase 3 clinical trials — CLARITY (NCT00213135), the CLARITY extension study (NCT00641537), and ORACLE-MS (NCT00725985), all of which demonstrated Mavenclad’s efficacy compared with a placebo.
Long-term outcomes with Mavenclad
The now completed Phase 4 trial CLASSIC-MS (NCT03961204) trial — conducted post-approval in a real-world setting — evaluated the long-term durability of Mavenclad for up to 15 years beyond the two-year regimen of the three Phase 3 trials.
The analysis focused on the long-term outcomes of 435 CLASSIC-MS patients, ages 32-79, who previously participated in CLARITY with or without enrolling in the extension study. All eligible CLASSIC-MS participants had received at least one course of Mavenclad tablets or a placebo in the previous studies.
A total of 394 (90.6%) patients were previously treated with Mavenclad and 160 of them completed the two-year regimen. The time since the last Mavenclad dose ranged from 9.3 to 14.9 years, with a median of 10.9 years.
Meeting its primary long-term mobility goal, CLASSIC-MS demonstrated that significantly more Mavenclad-treated patients weren’t using a wheelchair or weren’t confined to bed compared with those given a placebo in CLARITY (90% vs. 77.8%). Compared with those never treated with Mavenclad, those who received the two full years of treatment were 48% less likely to require a wheelchair or be bedridden when they entered CLASSIC-MS.
The trial also met its secondary long-term disability objective by showing that patients who received the therapy were more likely to not need walking assistance compared with those given a placebo (81.2% vs. 75.6%).
Mavenclad reduces need for subsequent DMTs
In a four-year responder analysis, more Mavenclad-treated patients didn’t need subsequent DMTs relative to a placebo (66.2% vs. 36.6%). No disease reactivation was seen in more of those exposed to the medicine than a placebo (50.3% vs. 26.8%).
The team also noted that participants with high relapse activity responded well to Mavenclad treatment.
Over the 10.9-year median follow-up, more than half (53.1%) of the CLASSIC-MS patients didn’t further use DMTs. Most of those who used other DMTs were treated with immune-modulating interferons (68.6%).
Compared with a placebo, Mavenclad treatment during CLARITY lowered the likelihood of further DMT use after the last CLARITY dose, with 55.8% of patients exposed to Mavenclad versus 26.8% in the never-exposed group receiving no subsequent DMTs.
Likewise, fewer Mavenclad-exposed patients received a second subsequent DMT than never-exposed patients (14.2% vs. 29.2%), as well as those who were given a third DMT (4.6% vs. 7.3%). The estimated median time until the first subsequent DMT after the last CLARITY dose was longer with Mavenclad than with a placebo (12 vs. 2.8 years).
Among the 200 patients who didn’t have a relapse since their last dose, about twice as many treated with Mavenclad were relapse-free relative to those given a placebo (48.0% vs. 26.8%). This finding was reflected in the annualized relapse rate for Mavenclad against a placebo (0.12 vs. 0.23 relapses per year).
Finally, at the beginning of CLASSIC-MS, the proportion of patients in active employment was higher among those exposed to Mavenclad in CLARITY compared to the never-exposed group (51% vs. 27.5%).
“Together, these findings support previous studies that have reported on the sustained efficacy of [Mavenclad] tablets following treatment,” the researchers said.
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