Phase 1 trial of NKX019 cell therapy in gMG patients cleared to open
CAR therapy uses NK immune cells, possibly safer than those based on T-cells
An investigator-initiated clinical trial will assess the safety and efficacy of NKX019, Nkarta’s investigational natural killer (NK) cell therapy for autoimmune diseases, in people with myasthenia gravis (MG).
The open-label Phase 1 trial will be led by researchers at the University of California, Irvine, and the University of Kansas Medical Center. The company received the go-ahead for the trial following the clearance of an investigational new drug application by the U.S. Food and Drug Administration.
The therapy also is being tested in patients with other autoimmune conditions, including systemic sclerosis, ANCA-associated vasculitis, and idiopathic inflammatory myopathy, participating in a separate and enrolling clinical trial.
“The expansion to these four autoimmune indications … speaks to the promise of our investigational NK cell therapy, NKX019, to provide a safe and accessible treatment option for people living with autoimmune disease,” Paul J. Hastings, CEO of Nkarta, said in a company press release.
NKX019 CAR cell therapy targets the CD19 protein on surface of B-cells
An autoimmune disease, MG is caused by self-reactive antibodies that mistakenly attack proteins at the neuromuscular junction — the site where nerve and muscle cells communicate to coordinate voluntary movements. These autoantibodies are produced by immune cells called B-cells.
“While the development of new therapies continues to improve outcomes for people living with myasthenia gravis, there remains considerable need for further improvements in clinical outcomes, as well as therapy administration,” said Ali A. Habib, MD, a professor of neurology at the California university and lead investigator of the MG trial.
“Most current therapies require ongoing and potentially life-long treatment. Cell therapy has the potential to move away from chronic dosing and change the treatment paradigm for people with myasthenia gravis,” Habib added.
Cell therapies that enable other immune cells to target and destroy B-cells are of particular interest in treating autoimmune diseases. These include CAR cell therapies, which are based on the principle of engineering immune cells in the lab to equip them with a chimeric antigen receptor (CAR) that allows them to recognize and destroy cells harboring specific protein markers, including B-cells.
NKX019 is a CAR cell therapy that uses NK immune cells, a type of white blood cell that is considered less likely to trigger an unwanted immune response than the immune T-cells commonly used in CAR therapies.
The therapy involves collecting NK cells from a healthy donor and modifying them in the lab with a CAR targeting CD19, a protein found on the surface of B-cells. The modified cells also contain at their surface a version of interleukin-15, an immune signaling protein, to help sustain their activity.
Phase 1 trial to evaluate safety, potential efficacy after three doses of therapy
The investigator-initiated trial will test the safety and potential efficacy of NKX019 in people with generalized MG, who will receive three doses of the therapy on days zero, three, and seven, following lymphodepletion with cyclophosphamide, a chemotherapy agent with established safety in people with autoimmune diseases. Lymphodepletion is a procedure that’s meant to lower the number of a patient’s immune cells, making room for the CAR cells and supporting their long-term activity.
Levels of autoantibodies, the profile of cytokines (immune signaling molecules), and the therapy’s pharmacokinetics (movement into, through, and out of the body) will also be evaluated.
NKX019’s safety, efficacy, and clinical activity currently are being assessed in the open-label Ntrust-1 trial (NCT06557265) enrolling people with lupus nephritis, a common lupus complication affecting the kidneys. Preliminary data from Ntrust-1 and the enrolling trial in other autoimmune diseases, called Ntrust-2, are expected in 2025.
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