ECTRIMS: Atara's off-the-shelf T cells for EBV-driven MS show promise in small study

Head with brain in cupped hand
Atara Biotherapeutics is developing two T-cell therapies that target Epstein-Barr virus in multiple sclerosis. (Pixabay)

Epstein-Barr virus (EBV) is thought to play a role in the development of some diseases, including multiple sclerosis. San Francisco-based Atara Biotherapeutics has been developing a cell therapy for MS that targets the virus, and it has results from a phase 1 study that its executives believe provide strong justification for larger studies of the approach.

The therapy, called AT188, is made of T cells that target and attack EBV-infected B cells. In the phase 1 trial, all six of the patients who received the highest of the two doses reported showed at least a partial improvement in MS symptoms at six months, while four of the six patients on the smaller dose showed a clinical decline. The company discussed the results at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Epstein-Barr is known to increase the risk of MS, and the virus has been found in the brains of patients with the disease at higher rates than it has in healthy people.

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Atara is developing two T-cell therapies that target EBV: ATA190, which is “autologous,” or derived from individual patients’ own immune cells; and ATA188, which is “allogeneic,” meaning it can be premanufactured from unrelated donor cells. The company is launching a phase 2 study of ATA190 this year and said at ECTRIMS that it has completed enrollment in the phase 1 trial of ATA188.

RELATED: Anti-cancer immune cells protect against MS in mice

T-cell therapies have so far made the biggest impact in oncology, with the FDA approvals of two treatments for blood cancer, Novartis’ Kymriah and Gilead Sciences' Yescarta. Both products are personalized in a complex process that involves removing T cells from patients and engineering them to be able to recognize and attack their cancers. The success of those treatments has inspired research aimed at applying the technology to other diseases—and simplifying it by developing off-the-shelf cells.

The early ATA188 trial was primarily designed to establish a safe dose of the cells in MS, but Atara also measured efficacy based on seven criteria including fatigue, visual acuity and walking ability. Atara hopes to show that its T-cell therapies can improve upon existing MS drugs, which suppress the out-of-control B cells that cause the disease’s disabling symptoms. Those drugs can slow the progression of MS, but they haven’t been shown to reverse its symptoms, Atara CEO Pascal Touchon said during a conference call with analysts after the presentation.

“While the immunosuppressive approaches may help to address some of the molecular and cellular dysfunctions that give rise to MS symptoms, they might not directly target the underlying pathogenesis of the disease,” Touchon said. Therefore there is a need for new approaches that “have the potential to stop or even reverse disease progression,” he added. Touchon headed up Novartis' oncology efforts before jumping ship to become CEO of Atara in May.

During the call, one analyst asked whether there were any differences between the two patient groups that could explain the results, aside from the dosage of cells each received. There were no demographic differences or other factors that would have caused the patients on the higher dose to respond better, said AJ Joshi, M.D., chief medical officer of Atara.

Another analyst wondered whether ultimately the company would investigate even higher doses than what’s planned for this phase 1 study. The trial would need to show a direct correlation between increasing the quantity of cells and an improvement in symptoms, Joshi said. “We’d really want a good reason to move higher on the dosing.”

When asked whether the company is using imaging technology to track the cells in the brain, Joshi said that would happen in larger, placebo-controlled studies. Atara plans to report detailed data from the phase 1 study next year and to identify the dose for a randomized, double-blind, placebo-controlled phase 1b study.

Amit Bar-Or, M.D., chief of the Perelman School of Medicine's MS division at the University of Pennsylvania, said in a statement that the early findings from Atara look promising. “The outcome classification using multiple clinically recognized MS scales is an innovative approach, and I look forward to advancing the study alongside my colleagues for progressive MS patients who have limited treatment options and where continual clinical decline is expected.”

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