MESEMS: No Reduction in MS Lesions With Stem Cell Therapy

Damian McNamara

September 11, 2019

STOCKHOLM — Autologous mesenchymal stem cell (MSC) treatment did not significantly reduce the number of gadolinium-enhancing lesions on imaging in patients with multiple sclerosis (MS) compared with placebo in a new multinational study.

"The results are clearly negative for the primary endpoint. There was no sign of an effect of mesenchymal stem cells over placebo at 24 weeks," noted lead author Antonio Uccelli, MD, PhD, professor of neuroscience at the University of Genoa, Italy.

However, a secondary outcome looked more promising. The investigators found that intravenous, bone marrow-derived MSC therapy demonstrated "an important trend toward decreasing annualized relapse rate over 24 weeks" compared with placebo.

These first results of the phase 2 Mesenchymal Stem Cells for Multiple Sclerosis (MESEMS) study were presented here at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Builds On Earlier Research

The current trial builds on findings from early phase 1 studies of MSCs in MS and other neurologic diseases that "demonstrated safety and a signal for efficacy," Uccelli told meeting attendees.

"We and many others provided evidence that this can foster neuroprotection and promote endogenous neurogenesis. But to move to clinical stage, we need to have compelling data from at least phase 2 studies," he added.

To compare early vs delayed treatment, the MESEMS investigators randomly assigned participants with active or relapse-remitting MS to stem cell treatment or to a control group at baseline. After 6 months, the crossover study design switched the patients to the other treatment group for another 6 months.

The study included 144 patients with MS, of whom approximately 45% had at least one gadolinium-enhancing lesion in the previous year. A total of 65% had relapse-remitting MS and 35% were in the progressive phase. Mean age was 39 years, 60% of participants were women, and the mean onset of MS symptoms was 7 years before study entry.

A total of 63 people completed the study in the group receiving MSC then placebo, and 71 in the placebo then MSC group. There was "no particular sign" to explain discontinuations, Uccelli said.

In terms of the primary outcome, the reduction of gadolinium-enhancing lesions in the stem cell group vs control group was not statistically significant (relapse rate [RR], 0.94; 95% confidence interval [CI], 0.58 - 14.9; P = .78).

A secondary endpoint, decrease in the annualized relapse rate (ARR) between groups, approached significance, Uccelli reported. "There was a 36% in the ARR" that favored active treatment over placebo (RR, 0.64; 95% CI, 0.36 - 1.14; P = .13)

"I am very glad to say we observed a signal — I would say a strong signal although not yet statistically significant — in a reduction of the annualized relapse rate," Uccelli said. The number of relapses was adjusted for gadolinium-enhancing lesions on a baseline scan.

Promising Safety

The presence of any adverse events was similar between groups.

"There is good news about safety, although we are all aware we are not going to do a treatment just because it is safe; but the number of adverse events did not differ significantly between treated and placebo subjects in the first 24 weeks," Uccelli said.

The rate of any serious adverse event (SAE) was approximately 10% in the study population. Most SAEs were grade 1 or 2, and there were no grade 4 SAEs reported. The SAEs "mainly occurred in placebo," with 12 cases vs 2 cases in the MSC group, Uccelli reported.

MESEMS involves investigators and participants from Italy, Canada, the United Kingdom, Denmark, Austria, Sweden, France, Iran, and Spain.

The researchers plan to continue evaluating the data for a number of secondary and exploratory outcomes, including active MRI lesions and T2 volume, and clinical parameters including disability progression on the Expanded Disability Status Scale.

"Further cause analysis will hopefully reveal whether MSCs are effective on other MRI and clinical parameters, as well as on any metrics that might suggest repair," Uccelli said.  

"Very Important," but Preliminary

Asked by Medscape Medical News to comment, session comoderator Jiwon Oh, MD, PhD, staff neurologist and scientist at the Keenan Research Centre for Biomedical Science at St. Michael's Hospital in Toronto, Canada said that this multicenter study is "very important because it evaluated something we don't yet have answers to."

"The results are still very preliminary. I'm looking forward to hearing more," she said.

Oh added that use of MSCs represents "a radically different" approach to treating MS.

Uccelli and Oh have reported no relevant financial relationships.

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract P1378. Presented September 11, 2019.

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