Phase 1 NMOSD Interim Results Show CAR T-cell Therapy Safe, Effective

CARTinNS is exploring single CT103A dose in up to 18 adults

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The CAR T-cell therapy CT103A appears safe generally and may ease disability and improve the quality of life in adults with relapsed or refractory neuromyelitis optica spectrum disorder (NMOSD) who test positive for antibodies against aquaporin-4 (AQP4), according to data from a small Phase 1 clinical trial.

“In this ongoing phase 1, first-in-human clinical study of CT103A … patients displayed a manageable safety profile and had a promising clinical response without any additional immunosuppressive therapy,” the researchers wrote.

The study, “Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results,” was published in Signal Transduction and Targeted Therapy. 

The study was funded by Nanjing IASO Therapeutics, CT103A’s developer, and the trial is being sponsored by and conducted at Tongji Hospital of the Huazhong University of Science and Technology, China.

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China OKs Clinical Testing of First CAR T-cell Therapy in NMOSD

T-cells are immune cells that can destroy other cells, such as virus-infected cells and cancer cells. Every T-cell is equipped with a specialized receptor protein that directs the immune attack.

CAR T-cell therapy involves equipping T-cells with laboratory-made receptors, called chimeric antigen receptors (CARs), that can direct the immune cells to destroy specific cell populations for therapeutic purposes.

CAR T-cells have shown promise in a number of cancers and researchers are exploring their potential in autoimmune conditions like NMOSD.

NMOSD is driven mostly by abnormal antibodies against AQP4, a protein on the surface of neuron-supporting brain cells, that drive an erroneous autoimmune response. Like other antibodies, anti-AQP4 antibodies are produced by a class of immune cells called B-cells.

CT103A is a CAR T-cell therapy wherein the CAR T-cells are equipped with receptors that direct them against BCMA, a protein on the surface of B-cells, ultimately promoting their death.

A Phase 1 clinical trial, called CARTinNS (NCT04561557), is exploring the safety and effectiveness of a single CT103A dose in up to 18 adults with relapsed or refractory antibody-driven neuroinflammatory disorders such as NMOSD.

Results of CAR T-cell therapy on first 12 patients

Interim findings from the first 12 patients treated in CARTinNS and followed for a median of 5.5 months (range, one to 14 months) have been reported. All were positive for anti-AQP4 antibodies, 10 (83%) were women, and their age ranged from 30 to 67.

All had been on immunosuppressive medications, but continued to have disease activity despite treatment, with a median of two NMOSD attacks in the year before enrolling in the trial.

During the trial’s dose-escalation portion, the first three patients received CT103A at a dose of 0.5 million CAR T-cells per kilogram of body weight and the following three were treated with 1 million CAR T-cells per kilogram.

Based on the favorable safety profile of the higher dose, an additional six patients were enrolled to the study’s expansion portion and given 1 million CAR T-cells per kilogram.

Because of their powerful inflammatory cell-killing capabilities, CAR T-cell therapies can be toxic. All the patients had severe or life-threatening side effects, with the most common being lower counts of immune cells and other blood cells. Most of these were resolved within a month.

All had mild to moderate cytokine release syndrome, an inflammatory side effect commonly marked by flu-like symptoms. More than half (58%) developed infections after treatment.

Treatment-related serious side effects included cytomegalovirus infection (25%), clotting disorders (8%), and pneumonia (8%).

“The overall frequency of treatment-related [serious side effects] was tolerable,” the researchers wrote, adding “the results observed with CT103A in NMOSD indicate a favorable safety profile.”

Blood analyses showed CAR T-cells were still detectable in all patients a month after treatment and in 17% of them after six months.

Reduction in anti-AQP4 antibodies, EDSS scores

Also, all the patients showed reduced blood levels of anti-AQP4 antibodies after CT103A treatment. These antibodies were undetectable in seven of 10 evaluable patients (70%) at three months post-treatment and in five of six evaluable patients (83%) at six months.

All but one patient (92%) had no NMOSD attacks since treatment, without additional immunosuppressive therapies. One had a possible attack of reduced visual acuity in the left eye, which occurred 14 months after treatment.

At last follow-up, all showed a score reduction in the expanded disability status scale (EDSS), indicating less severe disability. The researchers also reported that eight (67%) patients’ walking ability improved and nine (75%) had improved bowel and bladder function.

Patient-reported quality of life also generally improved after CT103A treatment.

The three NMOSD patients with other co-occurring autoimmune diseases — two with Sjögren’s syndrome and one with rheumatoid arthritis — also improved clinically in those conditions after treatment.

“Our data show that CAR-BCMA T-cell therapy might induce clinical remission of NMOSD associated with the rapid removal of AQP4 autoantibodies, and longer-term observation will be warranted,” the researchers wrote. “The follow-up to assess durability will continue for [two] years.”

The researchers emphasized that the trial is limited by its small size and said larger studies to assess the safety and effectiveness of CT103A and other CAR T-cell therapies in antibody-mediated diseases such as NMOSD are needed.