ATA188 is comprised of T cells that have been modified to selectively identify and eliminate cells infected by the Epstein-Barr virus (EBV), which may play a role in the MS disease process. ATA188 is an allogeneic T cell therapy, meaning that it was manufactured from healthy donors.
Phase I and II Trial: EMBOLD
EMBOLD is a two-part, phase I/II, multi-centre clinical trial testing the safety and efficacy of ATA188 in people with primary and secondary progressive MS. For Part 1 of the trial, 24 participants received one of four escalating doses of ATA188 and followed for one year to determine the optimal dose to use for Part 2 of the study. Among those who completed Part 1, 18 chose to enroll in its open-label extension phase in which participants are given one ATA188 infusion every year for up to four years.
Results from Part 1 showed that ATA188 was generally safe and well-tolerated across all doses. In particular, participants who received the two highest doses (20 and 40 million T cells) were more likely to achieve clinical improvements at one-year post-treatment.
New data collected after 3.5 years of follow-up further revealed that 20 of the 24 participants experienced a sustained stabilization (13 participants) or improvement (7 participants) in their functional disability as assessed by the Expanded Disability Status Scale (EDSS). Atara reported that the improvement in EDSS included return of previously lost functions such as the ability to walk unassisted or for longer distances. Additionally, compared to baseline, ATA188 treatment resulted in a significant increase of the MRI biomarker for myelin density (magnetization transfer ratio or MTR), suggesting that ATA188 could potentially facilitate myelin repair in people with progressive MS.
For Part 2 of the trial, up to 80 adults with primary and secondary progressive MS with evidence of past or current EBV infection will be randomized to receive two infusions of either placebo or an optimal dose of ATA188. At the one-year follow-up, participants in the placebo group will be given two infusions of ATA188 while those originally in the treatment group will be given one infusion of ATA188 and one infusion of placebo. After two years, participants will once again have the option to enroll in the open-label extension study, where they will receive ATA188 infusion once a year for up to three years.
The primary outcome measures for Part 2 will evaluate EDSS improvement at 12 months and secondary outcome measures will assess changes in MTR and other efficacy biomarkers. Participant recruitment for Part 2 of the EMBOLD trial is ongoing. The study is currently enrolling people with non-active progressive MS at select sites in Canada, the United States, and Australia. The anticipated study completion date is February 2026. For more information, please visit ClinicalTrials.gov
Pender, MP et al. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. Journal of Clinical Investigation (JCI) Insight. 2018; 3(22): e124714.
Pender, MP et al. Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis. 2020; retrieved from the European Charcot Foundation Annual Meeting poster presentation.
Atara Biotherapeutics. Atara EBV and MS Day. 2022; retrieved from Atara investor presentation.