FDA accepts IND for allogenic CAR T-cell therapy that could bypass lymphodepletion
The FDA has accepted an investigational new drug application for ALLO-329, an allogeneic chimeric antigen receptor T-cell therapy that may bypass lymphodepletion, paving the way for a phase 1 trial in lupus and other autoimmune diseases.
The trial will involve the use of Allogene Therapeutics’ Dagger technology, which aims to reduce, or avoid entirely, the need for pre-treatment lymphodepletion, a process that boosts the performance of CAR T cells but could be a barrier to patients receiving therapy, according to a press release from the manufacturer.
Joan T. Merrill, MD, a member of the Arthritis & Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, who is not involved with ALLO-329 or Allogene Therapeutics, told Healio the announcement reflects the current era of “clever innovations” in autoimmune disease.
“We are entering an era of increasingly clever innovations in medicine,” she said. “To the extent that an allogeneic cell therapy can be taken off the shelf and survive long enough in a patient to achieve its intended purpose, that would be significant progress.”
ALLO-329 targets CD19+ B cells and CD70+ activated T cells, both of which are key to immune dysregulation in autoimmune diseases. It achieves dual CAR expression using CRISPR-based site-specific integration, according to the release.
The acceptance of the IND application makes it possible for Allogene to commence a phase 1 basket study testing ALLO-329 in patients with systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies and systemic sclerosis. The trial, called RESOLUTION, is slated to start sometime in mid-2025, according to the release.
The trial will compare outcomes between patients who did not undergo lymphodepletion with those of patients on a dose of cyclophosphamide.
“Demonstrating the power of an allogeneic CAR T to reset the immune system, combined with the ability of our Dagger technology to reduce or eliminate lymphodepletion, could represent a transformative step forward,” David Chang, MD, PhD, president and CEO of Allogene, said in the release. “Successful proof-of-concept in this basket study has the potential to not only validate our best-in-class approach but also paves the way for expanding into a broad range of autoimmune indications beyond rheumatology.”
The FDA also recently granted fast-track designation to ADI-001, another allogeneic CAR T-cell therapy, for the treatment of relapsed or refractory class III or class IV lupus nephritis and SLE with renal involvement. ADI-001, developed by Adicet Bio, is a CD20-targeting gamma delta CAR-T therapy being advanced in SLE, SSc, idiopathic inflammatory myopathy, stiff person syndrome and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis.
A phase 1 study of ADI-001 for the treatment of lupus nephritis is now enrolling patients, and an ANCA-associated vasculitis trial is expected to begin enrollment in the second half of this year.
References:
Adicet Bio receives FDA fast track designation for ADI-001 for the treatment of refractory systemic lupus erythematosus with extrarenal involvement. https://www.businesswire.com/news/home/20250205155838/en/Adicet-Bio-Receives-FDA-Fast-Track-Designation-for-ADI-001-for-the-Treatment-of-Refractory-Systemic-Lupus-Erythematosus-SLE-with-Extrarenal-Involvement. Published Feb. 5, 2025. Accessed Feb. 7, 2025.
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