Atara, Imeka Team Up to Bring Advanced Imaging to ATA188 Trial
Atara Biotherapeutics has partnered with Imeka to use its proprietary biomarker imaging technology in the ongoing EMBOLD Phase 2 clinical trial, which is investigating ATA188 for the treatment of progressive forms of multiple sclerosis (MS).
The imaging technology will be used to determine if Atara’s ATA188 can effectively reduce inflammation and restore myelin in the brain and spinal cord of people with primary and secondary progressive MS (PPMS and SPMS). Myelin is a fatty substance surrounding nerve fibers that is key for efficient nerve cell communication, but is damaged in MS.
This will complement imaging data obtained in EMBOLD by other imaging techniques, including MRI scans measuring the magnetization transfer ratio (MTR), which detect subtle changes in brain structure.
“We are excited to collaborate with Imeka for our Phase 2 EMBOLD clinical study in progressive MS,” AJ Joshi, chief medical officer at Atara, said in a press release. “Their proprietary technology complements other imaging techniques, including MTR, which we are leveraging to analyze the effects of ATA188 on neuroinflammation and remyelination, key markers for disease progression. This work will contribute to the growing body of clinical knowledge around our investigational therapy.”
Imeka’s noninvasive biomarker technology combines artificial intelligence and free-water diffusion imaging to obtain detailed images of the brain’s white matter — regions composed mainly of nerve fibers and where most myelin is found. This helps clinicians visualize the degree of myelin loss and neuroinflammation and determine how well potential therapies work to reverse them.
“We are proud to collaborate with Atara Biotherapeutics on the search for innovation in the treatment of progressive MS,” Jean-René Bélanger, CEO of Imeka, said. “Biomarkers have potential to revolutionize the discovery and development of medicines for some of the most difficult-to-treat neurodegenerative diseases.
“Our proprietary non-invasive biomarker platform is a trusted resource for identifying biomarkers associated with MS and other conditions. By providing highly localized views of the effects of both disease and investigational treatments on white matter, we provide unique insights that can help pharmaceutical and biotechnology companies accelerate the development of potential new treatments through multiple phases,” Bélanger said.
Evidence suggests that the Epstein-Barr virus (EBV), a common type of herpes virus, can contribute to the onset and development of MS by infecting immune B-cells and causing them to wrongly produce antibodies that attack the myelin sheath.
While EBV infection is common in the general population, with about 90% of people becoming infected, studies have shown that virtually all MS patients have signs of EBV infection (past or present) at the time of their diagnosis.
ATA188 is a form of cell therapy in which T-cells — cells with the ability to fight infections and other threats — are collected from healthy donors and modified to kill B-cells and antibody-producing plasma cells that are infected with EBV.
The EMBOLD trial (NCT03283826) is evaluating the safety and efficacy of ATA188 in PPMS and SPMS patients. Enrollment is ongoing in the U.S. and Australia; more information about contacts and locations can be found here.
The trial has two parts. In part one, patients will receive increasing doses of ATA188 to determine the best dose for further testing, while part two will test the selected dose against a placebo.
In its first part, 25 patients received at least one dose of ATA188 and were followed for an initial 12 months. Among the 24 who completed that year in the trial, 18 chose to participate in its open-label extension (OLE) and continue receiving ATA188 every year for up to four years.
Recent data from part 1 and the OLE, covering a follow-up time of 33 months, showed that seven patients achieved a sustained disability improvement (SDI), a measure defined as improvements in the Expanded Disability Status Scale (EDSS).
Increased MTR values, indicative of fewer lesions and more normal-appearing brain tissue, were also seen in these seven patients.
EMBOLD’s part 2 is now enrolling about 80 PPMS and SPMS patients (with evidence of past or current EBV infection), who will be randomly assigned to ATA188 or a placebo infusion for one year. This is a crossover study, meaning that after one year, patients will switch treatment groups for another year.