Atara Biotherapeutics’ investigational ATA190, a cell therapy that wipes out immune B-cells infected with the Epstein-Barr virus (EBV), led to neurological improvements and reduced symptoms in patients with primary and secondary progressive multiple sclerosis (MS), a Phase 1 trial shows.
The trial results were published in the Journal of Clinical Investigation Insight in a study titled “Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.”
ATA190 is a T-cell immunotherapy that targets immune B-cells and plasma cells in the brain and spinal cord that have been infected with EBV. There is increasing evidence linking EBV infection with MS.
ATA190 is made from a patient’s own (autologous) immune cells, which are collected and modified in a lab to target the EBV-infected cells, then infused back into the patient’s blood. The goal is for the modified immune T-cells to recognize EBV-infected B-cells and kill them.
The Phase 1 trial (ACTRN12615000422527), conducted at the QIMR Berghofer Medical Research Institute and The University of Queensland, in Australia, evaluated the safety and efficacy of ATA190 as a treatment for progressive MS.
The study enrolled 10 patients — five with primary progressive MS (PPMS) and five with secondary progressive MS (SPMS). Patients had experienced progressive neurological deterioration due to MS for a mean of 10.1 years.
Participants were treated with four escalating doses of ATA190, administered intravenously over a period of eight weeks. The lowest and first dose was 5 million modified T-cells, followed by doses of 10, 15, and 20 million. Patients were followed for 27 weeks after the first infusion.
Results showed that ATA190 was well-tolerated, with no severe adverse events detected during the study. One patient experienced a potential treatment-related adverse event — dysgeusia, a distortion of the sense of taste.
Efficacy was measured by several parameters, including changes in the Expanded Disability Status Scale (EDSS) score, fatigue, as well as cognitive and other neurological parameters. Researchers also analyzed patients’ brains by magnetic resonance imaging (MRI) and tested their cerebrospinal fluid (CSF) — the liquid around the brain and spinal cord — for the presence of antibodies.
Seven of the 10 patients had improvements in neurological parameters — such as increased productivity, cognition, and word finding — accompanied by a reduction in symptoms. These benefits began two to 14 weeks after the first infusion.
Fatigue, one of the most disabling and hard-to-manage symptoms of MS, was reduced across the group — the median Fatigue Severity Scale score was lower at week 27 compared to the beginning of the study. This decrease, however, didn’t reach statistical significance.
Analysis of the CSF showed that levels of antibodies were reduced at the end of the study in four out of nine patients. Moreover, three of those four patients showed neurological improvements.
Patients received T-cells with different degrees of reactivity against EBV. Six patients who received T-cells with strong EBV reactivity showed clinical improvement; three of those experienced improvements in the EDSS score.
The other four patients received T-cells with weak EBV reactivity; of these, one showed improvement. None experienced a change in the EDSS score.
The team said that overall, the results show that the benefits seen are linked with T-cell effects.
“We previously presented promising initial ATA190 results in patients with progressive MS, and [now] the published results confirm our earlier observations,” Professors Michael Pender, of The University of Queensland, and Rajiv Khanna, coordinator of QIMR Berghofer Centre for Immunotherapy and Vaccine Development, the study’s lead authors, said in a press release.
“Findings from the study support growing evidence that targeting EBV-positive B-cells is a potential novel treatment modality for MS and merit additional investigation,” Pender and Khanna said.
“T-cell therapy targeting only EBV-infected B-cells is a treatment modality that could offer favorable safety and durable efficacy,” they wrote, adding that their work “sets the stage for further clinical trials with autologous and allogeneic EBV-targeted T-cell therapy in MS.”
Atara is developing another therapy, ATA188, to eliminate EBV-infected B-cells in the central nervous system. ATA188 uses immune cells from donors, not from the patients themselves — an allogenic therapy.
“We are also advancing an ongoing Phase 1 off-the-shelf, allogeneic ATA188 study in patients with progressive MS across clinical sites in the U.S. and Australia. We look forward to continued development of both programs, including our plans to initiate a randomized ATA190 MS study,” said Dietmar Berger, MD, PhD, global head of research and development of Atara Biotherapeutics.