Atara Biotherapeutics’ ATA3219, an investigational allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy consisting of Epstein-Barr virus (EBV)-sensitized T-cells that have not been genetically modified, has received clearance on an investigational new drug (IND) application from the FDA for a clinical trial in systemic lupus erythematosus (SLE) and lupus nephritis (LN).1
Atara is planning to conduct a phase 1 clinical trial for ATA3219 that will treat patients with SLE and LN. The multicenter, open-label, dose-escalation trial will utilize 3 different dose levels: 40x106 CAR+ T-cells, 80x106 CAR+ T-cells, and 160x106 CAR+ T-cells, with a group of 3 to 6 patients to be assigned to each dose level. The company anticipates that the first participant will be enrolled during the second half of this year. Participants will receive ATA3219 as a 1-time infusion after lymphodepletion. Atara expects to announce initial data from the trial in the first half of 2025.
“Existing therapeutic agents for LN yield suboptimal responses and have limitations due to their requirement for ongoing administration, susceptibility to treatment failures, and limited accessibility to inflamed tissues resulting in incomplete depletion of B-cells,” Rajani Dinavahi, MD, the chief medical officer of Atara, said in a statement.1 “CAR T-cells can naturally infiltrate deep into target tissues to mediate B-cell depletion and produce durable responses. Building on the encouraging academic data in LN with autologous CD19 CAR-T, ATA3219 is an off-the-shelf therapy that could significantly reduce constraints for patients and physicians like leukapheresis and long waiting times, therefore potentially improving access to a large population of patients.”
The submission of the IND application for ATA3219 was originally announced by Atara on February 14, 2024.2 The company noted that the IND application includes “robust” preclinical data showing that ATA3219 was able to achieve nearly complete CD19-specific depletion of B-cells from patients with SLE in vitro in comparison to controls. This IND clearance is the second for ATA3219, which previously received clearance of an IND application for evaluation in a phase 1 clinical trial (NCT06256484) for patients with relapsed/refractory B-cell nonHodgkin lymphoma (NHL).1 The trial in NHL was launched on January 22, 2024 and is currently recruiting patients according to the clinicaltrials.gov page.
Key Takeaways
- Atara Biotherapeutics’ ATA3219, an investigational allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy consisting of Epstein-Barr virus (EBV)-sensitized T-cells that have not been genetically modified, has received clearance on an investigational new drug (IND) application from the FDA for a clinical trial in systemic lupus erythematosus (SLE) and lupus nephritis (LN).
- The planned phase 1 trial will involve dose escalation with 3 different dose levels of ATA3219, with the first participant expected to be enrolled in the second half of the year. Initial trial data is anticipated to be announced in the first half of 2025.
- The IND application included preclinical data supporting its efficacy in CD19-specific B-cell depletion.
ATA3219 is not Atara’s first attempt to tackle an autoimmune or likely autoimmuneindication with T-cell therapy. The company was previously evaluating ATA188, an investigational allogeneic, EBV T-cell immunotherapy, in the phase 2 EMBOLD clinical trial (NCT03283826) for the treatment of multiple sclerosis (MS).3 Although, in November 2023, Atara announced that it was planning to discontinue EMBOLD after it failed its primary endpoint of showing superiority of ATA188 over placebo in patients with MS. As of February 23, 2024, the clinicaltrials.gov page for EMBOLD states that the study was terminated because the primary end point was not achieved.
"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,” Pascal Touchon, the president and chief executive officer of Atara, said in a November 2023 statement.3 “We are grateful to the patients and investigators who participated in the study, and to colleagues at Atara for their steadfast work. 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.”
REFERENCES
1. Atara Biotherapeutics receives FDA clearance of IND application in lupus nephritis for ATA3219, an allogeneic CAR-T therapy. News release. Atara Biotherapeutics, Inc. February 29, 2024. Accessed March 11, 2024. https://investors.atarabio.com/news-events/press-releases/detail/343/atara-biotherapeutics-receives-fda-clearance-of-ind
2. Atara Biotherapeutics announces submission of investigational new drug application for ATA3219 for treatment of lupus nephritis. News release. Atara Biotherapeutics, Inc. February 14, 2024. Accessed March 12, 2024. https://investors.atarabio.com/news-events/press-releases/detail/341/atara-biotherapeutics-announces-submission-of
3. Atara Biotherapeutics announces primary analysis data from phase 2 EMBOLD clinical trial of ATA188 in non-active progressive multiple sclerosis. News release. Atara Biotherapeutics, Inc. November 8, 2023. Accessed March 12, 2024. https://investors.atarabio.com/news-events/press-releases/detail/330/atara-biotherapeutics-announces-primary-analysis-data-from
