Efficacy, Safety of Mavenclad in Real World Similar to That of Trials
The safety and efficacy of the approved multiple sclerosis (MS) therapy Mavenclad (cladribine) in a real-world group of patients were similar to what had been demonstrated in clinical trials, a new study reports.
Among 243 people with relapsing-remitting multiple sclerosis (RRMS), more than 60% showed no evidence of disease — no relapses or worsening disability — nearly two years after the study’s start, according to researchers.
The team noted that Mavenclad was shown to work better in patients who had tried fewer previous therapies, supporting its use at an early point “along the treatment algorithm.”
“Real-world evidence from diverse population is extremely valuable in determining drug effectiveness and safety outside of the selected conditions of RCTs [randomized controlled clinical trials],” the team wrote. “Indeed, the complementary role of real-world evidence and RCTs findings in guiding decision making, widely acknowledged in clinical practice, has been recently recognized also by regulatory authorities.”
Mavenclad is a short-course oral therapy that works to block the growth of certain immune cells that drive MS. It has been approved in the U.S. and the European Union since 2017 for relapsing forms of the disease, though the therapy is usually only given to patients who have already tried other treatments because it carries a high risk of severe side effects. One such side effect, or adverse event, is lymphopenia, characterized by extremely reduced counts of lymphocytes, a class of immune cells.
Now, a team led by scientists in Italy reported real-world outcomes for people with MS who were treated with Mavenclad at one of eight centers in the country.
About two-thirds of the patients were female, and most (70.7%) were switching to Mavenclad from another MS treatment, mainly due to lack of efficacy with prior lines of therapy. In the year prior to starting Mavenclad, the average relapse rate was 0.69 relapses per year. Additionally, more than half of the patients (56.7%) had actively inflamed lesions when they started Mavenclad treatment.
Over a median follow-up time of nearly two years (22 months), 64% of the patients showed no evidence of disease activity — a status known as NEDA-3. It is defined as no relapses, no new or enlarging lesions on MRI scans, and no worsening disability. The median time to NEDA-3 loss was 2.6 years.
“We found high rates of NEDA-3 after 22 months of [Mavenclad] treatment,” the researchers wrote, noting that these findings are generally in line with the results of the clinical trials that served as the basis for Mavenclad’s approval.
Statistical analyses showed that patients who had previously been on other lines of treatment were significantly less likely to achieve NEDA-3 — by about 36% — compared with individuals who received Mavenclad as a first treatment. More prior treatments also were associated with a shorter time to loss of NEDA-3, regardless of the type of prior therapy.
“The only factor affecting the likelihood of retaining NEDA and the risk to experience new relapses was the number of prior treatments,” the researchers concluded, though they noted that, “this finding should be interpreted with caution, since demographical and clinical characteristics of naïve and previously treated patients were different and matching among the two groups was not performed.”
Severe lymphopenia was detected in 19 patients. Statistical analyses suggested that those who experienced severe lymphopenia had significantly reduced lymphocyte counts when they started on Mavenclad, compared with those who didn’t experience this acute side effect.
“The risk of developing [severe] lymphopenia was higher in patients with lower lymphocyte count at baseline, in line with previous reports on patients treated with [other approved MS therapies]. These data might be useful to stratify patients according to their risk of developing lymphopenia, guiding personalized therapeutic choices,” the researchers wrote.
Other rarer side effects reported among the patients included elevated liver enzymes, infections, skin irritation, and hair loss.
“Overall, in this [real-world] study we confirmed previous data on effectiveness and safeness of [Mavenclad] in RRMS. Moreover, we identified better outcomes in patients exposed to a lower number of previous DMTs [disease-modifying treatments], suggesting that [Mavenclad] might be more effective when [used] as an early treatment,” the scientists concluded.
Mavenclad is sold by EMD Serono (known as Merck KGaA outside the U.S. and Canada). The company was not directly involved in this study, though several of the researchers disclosed having received funding from EMD Serono.