EMBOLD Study of ATA188 in Progressive MS Is Given Go-ahead
Atara's therapy is designed to kill cells infected with the Epstein-Barr virus
An independent committee of experts has recommended that the Phase 2 portion of the EMBOLD clinical trial continue as planned without a sample size adjustment, following an analysis of safety and effectiveness data.
“We look forward to completing the EMBOLD study as we aspire to demonstrate a potentially transformative profile for ATA188 in patients with progressive MS who have high unmet need and limited options,” Pascal Touchon, Atara’s president and CEO, said in a company press release.
ATA188 is a T-cell-based therapy designed to kill cells infected with the Epstein-Barr virus (EBV). Best known as the cause of infectious mononucleosis (“mono”), an emerging body of evidence has shown a strong link between EBV infection and MS risk.
The Phase 1/2 EMBOLD trial (NCT03283826) is testing the experimental therapy’s safety and effectiveness in people with primary and secondary progressive MS (PPMS, SPMS). In the first portion of the trial, 24 patients were treated and followed for a year. The results indicated the treatment was well-tolerated and hinted it may promote remyelination, or myelin repair.
The second phase was planned to enroll 80 PPMS and SPMS patients who would be randomly assigned to receive ATA188 or a placebo for a year. The main goal of this part is to evaluate the treatment’s effect on Expanded Disability Status Scale (EDSS) scores after one year.
Like other clinical trials, EMBOLD has an Independent Data and Safety Monitoring Committee (IDSMC) — a group of independent experts tasked with reviewing data from the trial as it’s ongoing. IDSMCs ensure the safety of participants in clinical trials and make recommendations based on interim analyses.
Here, the IDSMC looked at EDSS data after six months as well as other clinical and biomarker data. The analysis was planned to take place before the study had enrolled 80 participants to determine if more participants might be needed for it to have statistical power to detect a treatment effect.
The IDSMC recommended that the study continue as planned, without adjusting its planned sample size.
“After reviewing the clinical and safety data available at the data cut-off, the IDSMC did not highlight any safety concerns in the ongoing study,” Jakob Dupont, MD, head of global research and development at Atara, said.
Most Phase 1 patients’ EDSS scores stabilized or improved, meaning their functional disability was either maintained or reduced. Analyses showed EDSS improvements at six months could predict improvements after one year.
The Phase 2 data, which examined 34 patients with at least six months of follow-up and 15 who were followed for at least a year, was not sufficient to draw conclusions about ATA188’s benefits after 12 months, however, the company said.
The committee “believes the six-month interim endpoint may be an inaccurate measure of the potential of this intervention in this condition,” it added.
The trial has now reached its target enrollment of 80 patients, and top-line data is planned to be announced in late 2023.
“Following the EMBOLD [interim analysis], we are proceeding with the IDSMC’s recommendation that the study continue to completion without sample size adjustment,” Dupont said. “We are pleased to have completed the target enrollment for the EMBOLD study and look forward to sharing the topline results as planned at an appropriate forum in October 2023.”