ATA188 fails to outperform placebo in EMBOLD clinical trial

ATA188, an experimental cell therapy targeting the Epstein-Barr virus, failed to outperform a placebo at easing disability levels in people with nonactive progressive forms of multiple sclerosis (MS), according to data from the Phase 2 portion of the EMBOLD clinical trial.

The medication also showed no signs of efficacy on certain disease biomarkers.

“We are surprised and deeply disappointed with the results of EMBOLD,” Pascal Touchon, president and CEO of the therapy’s developer, Atara Biotherapeutics, said in a press release.

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Because no benefit from treatment was observed, Touchon said that Atara likely will be stopping the EMBOLD study and substantially cutting back on expenses related to ATA188. The company said it plans to refocus its resources on other experimental treatments in other indications.

Epstein-Barr virus (EBV) has been identified as a major risk factor for MS. This virus causes infectious mononucleosis (more commonly known as mono) and also nonspecific childhood illnesses. Most people have been infected with EBV by the time they reach adulthood.

After an infection, the EBV virus lives in an inactive state inside of immune B-cells cells. ATA188 is a cell-based therapy containing another type of immune cell, T-cells, derived from healthy people who have been infected with EBV.

The therapy specifically contains T-cells that are primed to kill EBV-infected B-cells, with the hope that destroying the infected cells might slow the progression of MS.

Background of the EMBOLD clinical trial

The EMBOLD Phase 1/2 clinical trial (NCT03283826) tested ATA188 in people with nonactive progressive forms of MS, including secondary progressive MS (SPMS) and primary progressive MS (PPMS).

These types of MS are marked by symptoms that gradually worsen over time, independent of relapses. In this trial, however, only patients without a recent history of relapses or inflammatory brain lesions (nonactive) were included.

In the Phase 1 portion of the study, 24 patients were treated with ATA188 and were followed for one year. Results were promising, with roughly a third of patients showing notable improvement in disability, defined as a meaningful reduction in Expanded Disability Status Scale scores that is confirmed in a follow-up visit.

The Phase 2 part of the trial included 103 people with progressive MS. Participants were given either ATA188 or a placebo and followed for one year.

The study sought to show that more patients given ATA188 would experience confirmed disability improvement after one year. This goal was not met, however; 6% of patients on ATA188 showed disability improvement, as compared to 16% of those given a placebo.

Scientists at Atara now will analyze these data in-depth, in an attempt to understand why the proportion of patients given ATA188 who experienced disability improvement was so much lower in the Phase 2 part of the study compared with the Phase 1 portion.

Seeking answers to the placebo effect

Researchers also hope to determine why so many people given a placebo experienced disability improvement, as only about 4%-6% of patients would be expected to have improvement without treatment due to natural variations in disease severity over time.

These evaluations will determine the next steps for developing ATA188, according to Atara. However, the company said it is unlikely to continue the EMBOLD clinical trial.

“We are further evaluating the EMBOLD data as we continue to believe in the critical role EBV plays in MS [disease development], however we anticipate stopping the study as no treatment benefit was observed,” Touchon said.

“We are grateful to the patients and investigators who participated in the study, and to colleagues at Atara for their steadfast work,” he added.