FDA approves clinical testing of CAR T-cell therapy for AAV, other conditions
FT839, a dual-target treatment, destroys disease-driving immune cell
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The U.S. Food and Drug Administration (FDA) has cleared the start of clinical testing of FT839, Fate Therapeutics’ experimental off-the-shelf CAR T-cell therapy for ANCA-associated vasculitis (AAV) and other autoimmune disorders.
The company plans to launch a basket Phase 1/2 clinical trial to evaluate FT839 in combination with standard treatments in people with AAV, as well as those with lupus, systemic sclerosis, rheumatoid arthritis, and idiopathic inflammatory myositis. Basket trials are designed to test a single therapy across multiple conditions at the same time.
While the company did not disclose where the trial will be conducted, enrollment is expected to begin in the second half of this year.
“FDA clearance of the FT839 [regulatory application] is an important milestone that expands our off-the-shelf … CAR T-cell platform capabilities for the comprehensive treatment of autoimmune disease,” Bob Valamehr, PhD, president and CEO of Fate, said in a company press release.
FT839 targets multiple disease-driving immune cells
In autoimmune diseases, immune B-cells produce antibodies that mistakenly target the body’s own healthy tissue. In AAV, these self-reactive antibodies attack neutrophils, a type of immune cell, causing them to become overactive and leading to inflammation and damage to small blood vessels. Over time, this damage can affect organs such as the kidneys and lungs.
CAR T-cell therapies use the body’s own immune T-cells, which regulate immune responses, to destroy disease-driving cells. Healthy T-cells are collected and engineered to carry a protein receptor, called CAR, that binds to specific proteins in cells known to contribute to a given disease.
FT839 is a “dual-CAR” T-cell therapy, meaning it’s engineered to recognize and attack two different targets at once: CD19, a protein receptor found at the surface of B-cells, and CD38, a marker found on a broader range of activated immune cells, including B- and T-cells.
Because B-cells are not the only immune cell involved in autoimmune disease, FT839 is expected to clear this broader group of cells in a single treatment.
“By co-targeting CD19 and CD38, FT839 is uniquely engineered to eliminate the full spectrum of aberrant, disease-driving immune cells, including B cells, plasma cells [a form of mature B-cells], and activated T cells,” Valamehr said.
Therapy designed for on-demand treatment
Unlike most CAR T-cell treatments that require doctors to collect and modify a patient’s own cells, FT839 is an off-the-shelf therapy, meaning it’s made in advance and stored for on-demand delivery to patients. This way, patients can receive treatment without the weeks-long wait that personalized cell therapies usually require.
Moreover, T-cells in FT839 have 13 genetic modifications that are meant to help in the targeting of multiple disease-driving immune cells, boosting effectiveness, evading the person’s own immune system, and prolonging their survival in the body.
One of these modifications involves the Sword & Shield technology, which is intended to help the therapy survive in the body and keep working without requiring patients to undergo intensive conditioning chemotherapy. This treatment is typically given before CAR T-cell therapy to make room for the delivered, therapeutic cells.
All these edits “are designed to overcome key limitations of … patient-derived and … donor-derived CAR T-cell therapy, including manufacturing complexity, high cost, limited on-demand availability, and the requirement for intensive conditioning chemotherapy,” the release stated.
Developer believes therapy has potential in certain blood cancers
In preclinical studies, FT839 was shown to selectively eliminate immune cells thought to drive autoimmune disease, including B-cells, plasma cells, and activated T-cells. It also eliminated certain blood cancer cells. These effects were seen both when FT839 was used on its own and when it was combined with other types of treatments.
The upcoming basket Phase 1/2 study will assess the therapy’s safety, tolerability, and preliminary efficacy across five different autoimmune diseases. Participants will receive FT839 alongside standard of care, with or without conditioning chemotherapy.
“We look forward to initiating the basket portion of this exciting Phase 1/2 study across multiple autoimmune indications and to advancing a truly accessible treatment option for patients in need,” Valamehr said.
Fate also plans to evaluate whether FT839 could help people with two other autoimmune diseases, type 1 diabetes and multiple sclerosis, through separate, investigator-led trials. The company also believes that the therapy’s design may also have potential in certain blood cancers such as lymphoma, leukemia, and multiple myeloma.
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