Nkarta gets green light from FDA to test NKX019 cell therapy in AAV
Upcoming trial will test treatment candidate in 3 autoimmune disorders
The U.S. Food and Drug Administration (FDA) has given Nkarta the green light to launch a clinical trial testing its cell therapy candidate NKX019 in people with ANCA-associated vasculitis (AAV) and other autoimmune disorders.
The upcoming multicenter trial, dubbed Ntrust-2, is expected to initially recruit as many as 12 patients with AAV, systemic sclerosis, or idiopathic inflammatory myopathy — three autoimmune conditions mediated by immune B-cells. While the company did not disclose where the trial will be conducted, it noted that results are expected next year.
This marks Nkarta’s second investigational new drug (IND) application of NKX019 to be cleared by the FDA. The first allowed the launch of Ntrust-1, a U.S.-based trial testing the therapy in people with treatment-resistant lupus nephritis, a type of kidney inflammation. It arises as a complication of lupus, another B-cell mediated autoimmune disease.
“The clearance of our second IND in autoimmune disease broadens the development of NKX019 and enables us to evaluate three additional B-cell mediated diseases in parallel,” Paul J. Hastings, Nkarta’s president and CEO, said in a company press release.
“We have selected a [clinical research organization] to support Ntrust-2, and trial activation activities are underway,” Hastings added.
Therapy targets abnormal immune B-cells in AAV, other diseases
AAV and many other autoimmune diseases are marked by abnormal immune attacks against healthy cells and tissue that involve abnormal immune B-cells that produce self-reactive antibodies.
Treatment with NKX019 involves collecting, modifying, and re-infusing natural killer (NK) cells, another type of immune cell, to home in on B-cells and destroy them, without requiring additional immune molecules to enhance its activity.
The therapy’s manufacturing process starts with leukapheresis, a procedure in which whole blood collected from healthy donors is processed through a cell separator to separate immune cells, including NK cells.
The collected NK cells then are genetically engineered in the lab to produce a chimeric antigen receptor, or CAR, that recognizes CD19, a protein found at high levels on the surface of B-cells. The cells also are modified to carry IL-15, an immune signaling molecule that’s meant to help NK cells survive and stay active for longer.
The modified NK cells are then grown into the millions and stored frozen for off-the-shelf supply. Once thawed and infused into a patient’s bloodstream, they’re expected to destroy B-cells and cut the production of harmful antibodies, easing symptoms of AAV and other B-cell-medicated autoimmune disease.
“NKX019 is unencumbered by many of the safety, infrastructure and logistical challenges associated with existing cell therapy approaches,” Hastings said.
The dose-escalation Ntrust-2 trial will evaluate the safety and efficacy of two doses of NKX019 — 1 or 1.5 billion NK cells — in people with AAV, systemic sclerosis, also known as scleroderma, or idiopathic inflammatory myopathy.
NKX019 is unencumbered by many of the safety, infrastructure and logistical challenges associated with existing cell therapy approaches.
Efficacy will be assessed based on the proportion of each group of patients achieving sustained disease remission, where no symptoms appear for some time, after treatment.
Each treatment cycle will involve infusion of the therapy, at the assigned dose, on days 0, 3, and 7 following treatment with the medication cyclophosphamide. That medication is used to destroy a subset of immune cells that include B-cells and NK cells to make room for the newly infused NK cells.
According to Nkarta, this approach allows for flexible dosing, meaning that NKX019 may be administered on demand and repeated if needed.
“We are also exploring other opportunities to positively impact the treatment of different populations with autoimmune disease through collaborations with leading investigators,” Hastings said.
About the Author
