Mavenclad Continues to Demonstrate Sustained Efficacy, Safety in Patients with Relapsing Forms of MS, Post-hoc Analyses Show

Mavenclad (cladribine) tablets continue to show sustained efficacy and consistent safety in patients with relapsing forms of multiple sclerosis (MS), post-hoc analyses of a Phase 3 trial extension study show.

The findings are set to be presented in several posters during the 5^th Congress of the European Academy of Neurology (EAN) being held June 29 to July 2 in Oslo, Norway.

“The wealth of new data that we are presenting at EAN 2019, from both our approved medicines and our pipeline in MS, highlight our commitment to making further advances for people living with this chronic disease,” Luciano Rossetti, head of global research and development for the biopharma business of Merck KGaA, Darmstadt, Germany, said in a press release.

Mavenclad is a therapy developed and marketed by EMD Serono (known as Merck KGaA outside the U.S. and Canada) that works by reducing the number of immune cells in the patient’s bloodstream, which are the cause of nerve degeneration in MS.

It was recently approved by the U.S. Food and Drug Administration for the treatment of adults with relapsing forms of MS, including relapsing-remitting MS and active secondary progressive disease.

The safety and efficacy of Mavenclad tablets was assessed in the randomized, double-blind, placebo-controlled Phase 3 CLARITY trial (NCT00213135).

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Previous data from CLARITY revealed that Mavenclad tablets administered at a dose of 3.5 mg/kg of body weight reduced the six-month risk of disease progression (assessed by the expanded disability status scale, or EDSS) by 47% among treated patients. Furthermore, among a subgroup of high relapse activity plus disease activity (HRA+DAT) patients, the six-month risk of disease progression was reduced significantly by 82%.

During the EAN conference, the company is presenting findings from post-hoc analyses of the CLARITY extension study (NCT00641537). The main purpose of this study was to assess the long-term safety, tolerability, and clinical benefit of Mavenclad tablets among patients who completed the CLARITY trial.

Patients who enrolled in the extension study were randomly assigned to receive either Mavenclad tablets (3.5 mg/kg) or a placebo, for a period of two years. A subgroup of patients was also re-exposed to therapy during the third and fourth years of the extension study.

In the first poster, “NEDA-3 durability in CLARITY Extension in patients with relapsing multiple sclerosis receiving Cladribine Tablets,” researchers examined the percentage of patients achieving a disease-free status, based on NEDA-3 (no evidence of disease activity) — defined as no relapses, no six-month confirmed EDSS progression, and no new or active brain lesions.

Results showed that between the third and fourth year of the extension study, 46% of the patients treated with Mavenclad during CLARITY and with a placebo during the extension study achieved NEDA-3, while 48% of those who were originally treated with Mavenclad and continued treatment during the extension study attained the same outcome. Similar results were obtained between the fourth and fifth year of the extension study.

These findings indicate that patients who were originally treated with Mavenclad tablets in CLARITY maintained a status of disease-free activity, regardless of whether they received a placebo or continued treatment during the extension study.

In two other posters, “CLARITY Extension: Sustained efficacy in relapsing remitting multiple sclerosis following switch from Cladribine Tablets to placebo in patients with high disease activity at baseline” and “Severity and frequency of relapses in patients with relapsing-remitting MS treated with Cladribine Tablets in CLARITY and placebo in CLARITY Extension,” researchers analyzed the efficacy and sustainability of the patients’ clinical responses, as well as the frequency and severity of relapses experienced by Mavenclad-treated patients who took a placebo during the extension study.

Results showed that the annualized relapse rate (ARR) among this group of patients (0.15) was equal or similar to that of HRA+DAT (0.14) and non-HRA+DAT (0.15) patient subgroups in CLARITY.

In addition, ARRs of relapse events that required patient hospitalization or treatment with steroids among this group of patients (0.14) was similar to that of patients treated with Mavenclad during CLARITY (0.15) and much lower than that of patients treated with a placebo during CLARITY (0.35).

These findings indicate that the clinical efficacy of Mavenclad demonstrated in CLARITY can be sustained for long periods of time without further treatment.

Further analyses also revealed that among those who were younger than 45, treatment with Mavenclad significantly reduced the ARR (0.26) compared with a placebo (0.65). Among those who were older than 45, the ARR was lower in the treatment group (0.28) versus the placebo (0.55).

These results are presented in the poster titled “Efficacy of Cladribine Tablets 3.5mg/kg in patients with relapsing multiple sclerosis aged above and below 45 years; CLARITY and CLARITY Extension.”

In another presentation, “CLARITY/CLARITY Extension: Lymphopenia rates are consistent in patients with and without high disease activity at baseline,” researchers examined the rates of lymphopenia (low white-blood cell count) in HRA+DAT patients who were treated with Mavenclad during the first two years of the extension study, and in a subgroup of patients who were re-exposed to the therapy in the third and fourth years of the extension study.

They found that the rates of grade 3 (severe) and 4 (life-threatening) lymphopenia were similar between HRA+DAT and non-HRA+DAT patients who received Mavenclad for different periods of time.

Supported by these positive results, EMD Serono is planning a Phase 4 study, named CLASSIC-MS, whose main purpose is to analyze the long-term outcomes, durability of effect, and real-world treatment patterns in 1,946 patients who participated in CLARITY, its extension study, or the ORACLE trial (NCT00725985).

A feasibility survey performed in 2017 showed that most clinical centers (85%–96%) reported having the relapse data, information on treatment timing, resources, and interest to participate in CLASSIC-MS. Based on this feedback, the company is planning to re-enroll the first patient this year in CLASSIC-MS.

The design of the CLASSIC-MS study is presented in a poster titled “Rationale, design and feasibility assessment of the phase IV CLASSIC-MS study evaluating long-term efficacy outcomes for patients with multiple sclerosis treated with Cladribine Tablets.”