Merck Extension Study Confirms Mavenclad’s Long-term Benefits in Relapsing MS Patients

Three-fourths of relapsing multiple sclerosis (MS) patients who took two short courses of Mavenclad (cladribine tablets) over two years remained relapse-free for four years, according to newly published data from the medication’s Phase 3 extension trial.

Moreover, patients who took Mavenclad during the first two years and then a placebo for the next two years fared similarly to those who took Mavenclad for the entire four-year period.

The report, “Safety and efficacy of cladribine tablets in patients with relapsing–remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study,” appeared in the Multiple Sclerosis Journal.

“Today’s publication further strengthens the evidence for the use of Mavenclad in MS, demonstrating significant, durable benefits in patients not receiving active treatment after the two short courses,” lead investigator Gavin Giovannoni, chair of neurology at Barts and The London School of Medicine and Dentistry, said in a press release.

The European Commission approved Mavenclad — developed by Merck KGaA (known as EMD Serono in North America) — to treat relapsing forms of MS in Europe on Aug. 25. It based that approval on data from the Phase 3 CLARITY (NCT00213135), CLARITY EXTENSION (NCT00641537) and ORACLE-MS (NCT00725985) trials, as well as the Phase 2 ONWARD trial (NCT00436826), and the ongoing long-term study PREMIERE (NCT01013350).

Besides showing the long-term impact of two short courses of Mavenclad — patients took tablets for a maximum of 20 days over two years — this latest study showed that continuing treatment into the third or fourth year offered no additional benefits.

This finding supports Merck’s earlier studies, which suggested that Mavenclad resets the immune system. This is a stark contrast in treatment approach to most approved MS drugs, which work by suppressing either T- or B-immune cells over the long term.

“The data from this publication and other recent articles suggest that Mavenclad selectively targets the adaptive immune system, particularly the B-cell compartment, and therefore allows the immune system to reconstitute while still preventing MS disease activity in the majority of treated patients,” said Giovannoni.

The CLARITY EXTENSION study included 806 patients who had completed the CLARITY trial. In the first study, patients had been randomly assigned to receive one of two Mavenclad doses (3.5 or 5.25 mg/kg body weight) or a placebo. In the extension study, patients who had been on active treatment were again randomized to receive further Mavenclad or a placebo.

By the end of the extension, 75.6 percent of patients who had received a cumulative dose of 3.5 mg/kg Mavenclad in the first study, and then a placebo in the extension, remained relapse-free. Meanwhile, 81.2 percent of those who were treated with Mavenclad in both studies had not experienced relapses.

Three-month disability progression, measured by the Expanded Disability Status Scale (EDSS), was absent in 72.4 percent of those treated with a placebo in the extension period, and 77.4 percent of patients who took Mavenclad for all four years.

Researchers also deemed safety to be similar in the two groups. Most adverse events were mild or moderate, and most patients who had their B-cells and T-cells depleted in the first part of the study had normal, or nearly normal, levels at the end of the extension.

Shingles were most common in patients who received the highest cumulative dose of the drug, affecting 4.8 percent of participants. But in the remaining treatment groups, rates of the viral infection were similar at 1.1 to 2 percent, researchers said.

“Today’s data add to the growing evidence for the use of Mavenclad in patients with relapsing MS,” said Luciano Rossetti, head of global research and development for the Merck’s biopharma business.

Besides Merck’s own studies, an independent study recently demonstrated that Mavenclad also improves patients’ quality of life. As such, the company plans to file regulatory approval for Mavenclad in the United States and elsewhere.