ATA188 and the Quest for Progressive MS Treatment

15 November 2023

Exploring the Connection Between Progressive MS and EBV

Multiple sclerosis (MS) is a complex and challenging neurological disorder affecting 2.8 million people worldwide. Among them, approximately 1 million live with continuous clinical decline and worsening disability, known as progressive MS. Whilst the exact triggers of MS are not fully understood, researchers believe a combination of genetic and environmental factors, including infection with Epstein-Barr virus (EBV), plays a pivotal role in its development.

What Does Previous Research Tell Us?

In the pursuit of effective therapies for progressive MS, the work of MS Australia-funded researcher Professor Michael Pender, a neurologist and researcher from The University of Queensland and Royal Brisbane and Women’s Hospital, has been key. His research revealed that in MS, one of the key cells of the immune system, called a T cell, demonstrated reduced effectiveness in killing EBV-infected cells. Collaborating with viral immunologist, Professor Rajiv Khanna, the team devised a method to “re-train” T cells, making them more responsive to EBV. This innovative therapy demonstrated promise in initial studies, although its production proved resource-intensive, necessitating the creation of a new cell product for each individual.

Atara Biotherapeutics Develops a New Therapy

To address this challenge, Atara Biotherapeutics developed ATA188, an ‘off-the-shelf’ T cell therapy derived from a small pool of blood donors. Unlike its predecessor, this treatment can be prepared for administration significantly faster, offering a potentially more streamlined and scalable approach. A clinical trial was initiated to evaluate the safety and efficacy of ATA188, focusing on people with primary or secondary progressive MS. The trial also aimed to assess disability improvement, with a group of 103 participants monitored for up to four years.

New Results Question Initial Hopes

Recent results have cast a shadow over the initial optimism surrounding ATA188. Atara Biotherapeutics announced that the experimental cell therapy failed to meet expectations in the EMBOLD Phase 2 study. The results from EMBOLD were unexpected, considering the encouraging results from the Phase 1 study, which showed a 33% improvement in disability for individuals on ATA188. In the EMBOLD study, individuals allocated to the group receiving the ATA188 active medication exhibited only a 6% disability improvement, while those allocated to the placebo (no active medication) comparator group experienced a 16% improvement. Atara is currently conducting a thorough review of the comprehensive dataset and these evaluations will guide Atara in determining the next steps in the ATA188 pipeline.

Paving the Future Path in MS Research

Despite the recent setback, it’s important to reflect on the insights gained from this study. Firstly, safety data from the study indicated no new safety concerns, confirming the positive safety profile previously observed with ATA188. Accumulating safety data in this field is much needed.

Additionally, it is important we recognise the significant role MS Australia plays in advancing innovative research, such as in the development of ATA188. Professor Michael Pender, supported by MS Australia funding, has been a trailblazer, laying the groundwork for a creative approach focused on addressing EBV-infected cells.

While the outcomes of the EMBOLD study may be disheartening, knowing what might not work (negative results) is also important in the pursuit of new treatments for MS. Understanding the limitations and challenges encountered in this study contributes valuable insights to the broader research landscape. MS Australia remains committed to supporting groundbreaking research that brings us closer to better treatments for people living with MS.

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ATA188 and the Quest for Progressive MS Treatment