Disease remission achieved in SLE with dual-target CAR T-cell therapy
Nearly all patients in small trial see long-term medication-free remission
Nearly all people with systemic lupus erythematosus (SLE) treated with iCell Gene Therapeutics’ dual-target CAR T-cell therapy achieved medication-free disease remission, according to long-term follow-up data from a small Phase 1 trial.
Further, kidney function continued to improve among those with lupus nephritis (LN), a common SLE complication involving the kidneys. A complete kidney response was seen among those diagnosed with LN fewer than 10 years previously.
Based on these findings — presented earlier this month at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress, in Vienna — iCell plans to seek permission in the U.S. and China to conduct additional clinical studies.
“It is exciting to see the continued progress over time in patients with lupus nephritis treated with iCell’s [CAR T-cell therapy],” Yupo Ma, MD, PhD, iCell’s founder and chief scientific officer,” said in a company press release. “We are excited to progress this therapy in clinical development and plan to file [regulatory applications requesting authorization to initiate new clinical trials] in the United States and China soon.”
Phase 1 trial in China tested CAR T-cell therapy in 13 SLE patients
SLE is an autoimmune disease in which self-reactive antibodies, called autoantibodies, attack healthy tissues in the body. In LN, autoantibodies target and damage the filtering units of the kidneys, leading to symptoms such as weight gain and swelling, an increase in urination, and high blood pressure
CAR T-cell therapies use T-cells — a type of immune cells that are capable of attacking and destroying other cells — isolated from patients or healthy donors. These cells are modified with a lab-made chimeric antigen receptor, or CAR, to attack a specific target.
iCell’s dual CAR T-cell therapy targets two proteins — CD19 and BCMA — found on B-cells and long-lived plasma cells, two types of immune cells that generate disease-driving autoantibodies. Its goal is to deplete B-cells, lower autoantibody levels, ease lupus symptoms, and prevent organ damage.
Conducted in China, the small Phase 1 study (NCT04162353/NCT05474885) included 13 SLE patients, 11 of whom had LN with active disease and had failed multiple lines of therapy. All participants stopped other lupus medications before receiving treatment in this trial.
The newly presented data reported the outcomes of 12 SLE patients who had been followed for a mean of 20 months, or nearly two years, and 10 LN patients who had been followed for a mean of 16 months, or slightly shorter than 1.5 years.
Blood tests revealed that B-cells were depleted entirely within 10 days of treatment in the 10 LN patients, with antibody depletion occurring within 42 days. All SLE patients were negative for all autoantibodies, including those produced by plasma cells, three months after receiving CAR T-cell therapy.
So far, all 12 patients continue to be medication-free with no relapses, according to the company.
Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores, a measure of disease activity, dropped from 9.9 points at the study’s start, or baseline, to 2.3 points at three months. All 12 patients scored zero on the Physician Global Assessment (PGA), a measure of disease activity and treatment response.
All but one of the dozen patients (92%) achieved complete remission based on the DORIS criteria, defined as an SLEDAI-2K score of zero, a PGA score of less than 0.5, and the use of no glucocorticoids and no immunosuppressants and/or biologic agents. This was up from nine patients recently reported in a published manuscript.
Complete kidney response seen for all LN patients diagnosed in prior 10 years
All six patients diagnosed with LN fewer than 10 years before had a complete kidney response, with the mean 24-hour urine protein level dropping by more than 90% from baseline. Treatment also improved kidney function in two of the four patients who had been diagnosed with LN more than 10 years prior or who had chronic kidney disease.
“Eleven patients are in complete remission, with all elevated autoantibodies and lupus symptoms eliminated, and the ongoing improvement in kidney function and recovery from lupus renal damage in these patients is encouraging,” Ma said.
Overall, the therapy was well tolerated, with no neurotoxicity observed. Cases of cytokine release syndrome, a serious immune response that commonly occurs with these therapies, were mild and resolved with treatment. Other than COVID-19, only one mild urinary tract infection was reported among patients.
"Our BCMA CD19 targeted cell therapy proof-of-concept study is the only trial of which we are aware that has demonstrated the safe elimination of all autoantibodies, delivering complete remission in the vast majority of patients. … We are hopeful these results will translate into the breakthrough needed for patients with lupus and other autoimmune diseases."
Greg Deener, CEO of iCell, said the company’s “differentiated approach … has the most mature safety database among autoimmune cell therapy candidates.”
“Our BCMA CD19 targeted cell therapy proof-of-concept study is the only trial of which we are aware that has demonstrated the safe elimination of all autoantibodies, delivering complete remission in the vast majority of patients,” Deener said. “We are hopeful these results will translate into the breakthrough needed for patients with lupus and other autoimmune diseases.”
No specific timeline was given by the company for seeking clinical trial authorizations.
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