The phase 2 EMBOLD study on ATA188, an allogenic T-cell immunotherapy for non-active progressive multiple sclerosis, did not meet its primary endpoint of confirmed disability improvement after 12 months of treatment.
Newly announced data from the phase 2 EMBOLD study (NCT03283826) showed that ATA188 (Atara Bio), an allogenic T-cell immunotherapy, did not meet its primary end point of change in confirmed disability improvement (CDI) among patients with non-active progressive multiple sclerosis (PMS) after 12 months of treatment. While the therapy showed a favorable safety profile, it did not demonstrate impacts on fluid and imaging biomarkers.
In its announcement, Atara described a 6% disability improvement observed in the 12-month findings, significantly lower than the 33% observed in the phase 1 study. In addition, the expected CDI rate for patients on placebo was 16% at 12 months, which was also greater than the 4% to 6% expected rate. In addition to continuing to review the data, Atara plans to reduce its expenses on ATA188 and invest greater resources on its differentiated allogenic CAR-T pipeline and executing its expanded tab-cel partnership with Pierre Fabre.
"We are surprised and deeply disappointed with the results of EMBOLD, particularly for the MS patient community which is in urgent need of new treatment options. We are grateful to the patients and investigators who participated in the study, and to colleagues at Atara for their steadfast work," Pascal Touchon, president and chief executive officer at Atara, said in a statement.1 "We are further evaluating the EMBOLD data as we continue to believe in the critical role EBV plays in MS pathogenesis, however we anticipate stopping the study as no treatment benefit was observed."
EMBOLD, a multi-national, randomized, double-blind, placebo-controlled study, included 103 adults with non-active primary or secondary PMS with primary end point observed after 12 months. After 1 year of treatment with either ATA188 or placebo, the study is designed so that all patients receive active therapy for an additional year. Following year 2, all participants can continue in a 3-year open-label extension during which they will receive annual treatment with ATA188. Atara did not specify whether patients in the study would continue treatment since the primary end point was not met.
ATA188 is unique in that it targets Epstein-Barr virus (EBV)-infected B cells and plasma cells in the central nervous system that may catalyze autoimmune responses and MS pathophysiology. In recent years, more research has solidified the idea that EBV is the leading cause of MS. In 2022, a study led by Albert Ascherio, MD, DrPH, et al included more than 10 million veterans and found a 32-fold increase in MS incidence in patients who’ve contracted EBV.2
In an open-label extension of a phase 1 study, ATA188 was shown to have a sustained clinical benefit that lasted over 39 months. In 7 of the 8 patients enrolled, sustained disease improvement that was steady at all time points was observed, with the most SDI driven by improvement in Expanded Disability Status Scale (EDSS) scores. For those with sustained EDSS improvement (n = 7), the magnetization transfer ratio (MTR) for unenhancing T2 lesions was improved at 6 months (P = .0796) and significantly improved at 12 months (P = .0213) compared with those without sustained EDSS improvement (n = 15). Overall, trends supported a correlation between increase in MTR signal and improvement in EDSS score as early as 6 months.3
Of the 24 patients who received ATA188 treatment and for whom efficacy was evaluated in the initial 12-month period, 18 chose to participate in the OLE and were followed for up to 39 months, with a data cutoff of August 2021. Among the 9 patients who achieved SDI, 7 did so in the initial 12-month period while the remaining 2 achieved SDI in the OLE phase. In total, 1 patient with secondary progressive MS who had achieved SDI experienced a nontreatment-related relapse at 18 months, approximately 6 months after their last ATA188 dose. This patient elected to discontinue the study.
A relationship between dose-escalation and increasing clinical response was observed, with the majority of the patients that achieved SDI (n = 7; 77.7%) receiving the 2 highest doses either initially or in the OLE, while 2 patients (22.2%) received the 2 lower doses. Eight patients that achieved SDI participated in the OLE, with a median time of maintained SDI of 18 months (range 0.03–27.0).
"Looking ahead, we maintain our strong conviction in the potential of our pipeline reinforced by the first ever regulatory approval of an allogeneic T-cell immunotherapy, EBVALLOTM, in Europe,” Touchon added.1 "Following anticipated additional payments and significant double-digit royalties from the recently expanded tab-cel® partnership with Pierre Fabre, we are currently well positioned with a cash runway well beyond upcoming milestones, including pre-clinical data for ATA3431 at ASH in December, preliminary clinical data from our Phase 1 study of ATA3219 in relapsed/refractory B-cell non-Hodgkin’s lymphoma anticipated in the second half of 2024, and expanding ATA3219 development into autoimmune disease."