Early Safety Data from Phase 1 Study of Immunotherapy in Progressive MS Patients To Be Detailed at EAN
Early, positive safety results from a Phase 1 trial testing a potential immunotherapy, ATA188, in people with progressive multiple sclerosis will be detailed at the 5th Congress of the European Academy of Neurology (EAN) late next month, its developer, Atara Biotherapeutics, announced.
ATA188 is an investigational and “off-the-shelf” (allogenic) T-cell immunotherapy designed to target Epstein-Barr virus-infected B-cells, which are believed to play an important role in the development of MS. A similar immunotherapy with autologous (patient-derived) T-cells, called ATA190, was previously shown to result in clinical improvements in a small number of progressive MS patients.
The Epstein-Barr virus (EBV) infects, activates, and expands B lymphocytes, the immune cells that produce antibodies. People with MS show what is believed to be a genetically determined deficiency in T-cells, which would normally kill EBV-infected B-cells.
This deficiency leads to higher EBV infection of B-cells. Scientists believe some of these EBV-activated and expanded B-cells are autoreactive, meaning that they can produce pathogenic autoantibodies against myelin (the protective coat of nerve fibers that is destroyed in MS patients).
ATA188 consists of allogeneic T-cells that are injected into MS patients to help kill EBV-infected B-cells. Allogeneic means that the T-cells are produced in the lab from donors unrelated, and genetically dissimilar, to the patient.
Some advantages of using allogeneic T-cells are that they are available immediately (hence, “off-the-shelf”), and that they show more consistent specificity and activity than autologous cells, individually derived from each MS patient.
The primary goal of the ongoing Phase 1 study (NCT03283826) is to evaluate the safety and tolerability of increasing doses of ATA188, and to identify a recommended dose for a later Phase 2 trial.
The study is expected to enroll between 24 and 30 primary and secondary progressive MS (PPMS, SPMS) patients in the U.S. and Australia. People with relapsing-remitting MS (RRMS) will also be recruited. Enrollment information, including contacts and locations of trial sites, can be found here.
Initial safety results showed that ATA188 was well-tolerated by people in the first two groups of treated patients, with no dose-limiting toxicities or serious treatment-emergent adverse events.
“We are encouraged by the initial ATA188 safety results from the first two dose cohorts,” Dietmar Berger, MD, PhD, global head of research and development of Atara Biotherapeutics, said in a press release.
“We recently progressed to dosing patients with progressive MS in the fourth and final planned dose escalation cohort, and look forward to presenting additional ATA188 safety results from this study at EAN in June,” Berger added.
Following the dose-escalation phase, a dose-expansion period is planned. This means that once the maximum-tolerated dose (MTD) — the ideal and recommended dose — has been identified, an additional number of patients will be treated with that dose.
Secondary study goals are preliminary evidence of treatment effectiveness, using measures of clinical improvement such as changes from the trial’s start in Expanded Disability Status Scale (EDSS) scores and magnetic resonance imaging (MRI) data.
The early safety data will be presented at EAN on June 30, in a poster titled “Preliminary phase 1 safety of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus (EBV)-targeted T-cell immunotherapy for patients with progressive multiple sclerosis (MS).” This 5th EAN congress opens in Oslo on June 29 and runs through July 2.