Phase 1 trial of SC291, CAR T-cell therapy for AAV, enrolling in US
Study testing treatment targeting B-cells in adults with GPA and MPA
A Phase 1 clinical trial assessing SC291, an experimental CAR T-cell therapy that Sana Biotechnology is developing for ANCA-associated vasculitis (AAV) and other autoimmune diseases, is recruiting patients at a number of sites across the U.S.
Called GLEAM (NCT06294236), the study started enrolling up to 36 adults, ages 18-75, last year at two sites: one in Aurora, Colorado, and the other in Seattle. It since has opened three additional sites in Atlanta, Baltimore, and Boston.
Eligible AAV patients are those with granulomatosis with polyangiitis or microscopic polyangiitis — the two most common types of AAV — who’ve either failed to respond to or relapsed after previous therapy. The trial also will include adults with certain forms of lupus, another autoimmune disease that, similar to AAV, can affect the kidneys.
“We expect to share clinical data later this year from two clinical-stage programs, SC291 and SC262 [Sana’s candidate for certain cancers],” Steve Harr, MD, Sana’s president and CEO, said in a company press release reporting on 2024 financial results and recent updates.
Depleting B-cells is expected to lower damaging autoimmune attacks
Autoimmune diseases occur when the immune system produces antibodies that mistakenly react against healthy tissue, triggering an immune attack that causes damage. Antibodies, including self-reactive ones, are produced by immune B-cells.
In AAV, self-reactive antibodies prompt white blood cells called neutrophils to guide an immune attack against the lining of small blood vessels, which become damaged over time. Disease symptoms can be evident in the kidneys, the lungs, and other organs.
SC291 is a CAR T-cell therapy designed to ease the severity of AAV and other B-cell-mediated autoimmune diseases by targeting and killing B-cells.
To prepare SC291, immune T-cells from a healthy donor are modified in the lab to produce a chimeric antigen receptor (CAR) protein that binds to CD19, a protein present at the surface of B-cells.
The modified cells then are infused into a patient. Once they bind to CD19, the cells are expected to promote B-cell death, reducing the production of self-reactive antibodies and easing symptoms.
To prevent the patient’s immune system from rejecting donor T-cells, Sana uses a so-called hypoimmune approach whereby donor T-cells are stripped of proteins that may be interpreted as foreign by the immune system. At the same time, these donor cells are modified to produce more of a specific protein that signals the patient’s immune system not to attack them.
Safety and tolerability are main trial goals, signs of efficacy also assessed
The GLEAM study is evaluating the safety, tolerability, and preliminary clinical response of a single infusion of SC291 into the bloodstream.
Enrolled patients will be given a chemotherapy mix of cyclophosphamide and fludarabine to wipe out their T-cells and make room for the modified CAR T-cells. All will be followed for up to two years after a SC291 infusion.
The trial’s main goal is to assess the proportion of patients experiencing adverse events and dose-limiting toxicities. Secondary goals include assessing how well patients’ kidneys are working, the length of time disease remission is achieved without a need for further therapy, and how long it takes for symptoms to return.
In the group of AAV patients, preliminary clinical response also will be measured by watching for changes in the Birmingham Vasculitis Activity Score (BVAS), a measure of disease activity, and by the proportion of patients achieving remission, defined as a BVAS of zero.
Blood levels of SC291’s CAR T-cells will be measured in all patients.
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