Bristol Myers Squibb has linked its CD19-directed CAR-T cell therapy to sustained clinical responses in people with systemic lupus erythematosus (SLE), providing further evidence that the emerging class of candidates can reset the immune system.
Interest in using CAR-T cell therapies has taken off since German researchers posted data on five people with SLE in 2022. An update on the study in February showed eight SLE patients remained in remission. Patients had severe, progressive disease that was resistant to standard immunomodulating treatments. The researchers also reported data in systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM).
BMS is part of a wave of drug developers, both large and small, that hustled CD19-directed CAR-T cell therapies into autoimmune trials in the aftermath of the initial SLE data drop. The Big Pharma is sharing data at ACR Convergence 2024, where it is presenting results that go beyond the existing abstract.
The expanded data set includes 11 patients with SLE as well as three with SSc and one with IIM. BMS saw complete peripheral B cell depletion in all evaluable SLE patients after the administration of its therapy, BMS-986353. B cells began to return in people with three months of follow-up but were mainly naïve cells, BMS said, with very few memory B cells, CD11c+ double negative B cells or plasmablasts.
B-cell depletion could reset the immune system, reducing patients' ongoing symptoms and freeing them from the need to keep taking medicines to manage their conditions. BMS reported clinical responses in the seven SLE patients with at least one month of follow-up.
The median score on the SLEDAI measure of SLE disease activity fell 10 points, causing most patients to fall from the high to mild or moderate parts of the scale. Similarly, median scores on an assessment of SLE by physicians and a quality of life tool fell 82% and 60%, respectively. All the SLE patients remained off therapies and free from signs of new disease activity after up to 11 months of follow-up.
One outstanding question is how many autoimmune patients will be willing to undergo CAR-T therapy. The safety profile of the candidates will shape the answer. BMS saw grade 3 or 4 treatment-emergent adverse events in 11 of the 15 patients in the safety data set. Neutropenia, meaning low levels of a type of white blood cell, was the most common grade 3 or 4 adverse event.
One patient had a grade 3 case of immune effector cell-associated neurotoxicity syndrome (ICANS), an adverse event associated with CAR-T therapy, on day 8. The patient had “waxing and waning mental status” and “decreased level of consciousness,” but the symptoms resolved by Day 10 after the doctors took her off confounding medications and gave treatments for ICANS.
BMS is now escalating the dose to determine the optimal level for a planned phase 2 study. Striking the right balance between safety and efficacy will be key, both because it will make the treatment attractive to more patients and because BMS-986353 may need to be at its best to match or beat rivals.
Kyverna Therapeutics has gathered a relatively large data set, in terms of patients, duration and diseases, but suffered a setback when a lupus nephritis patient relapsed after five months. Cabaletta Bio is running trials in SLE and other indications. On the Big Pharma side, BMS is joined by Novartis, which is expanding development of YTB323 into multiple sclerosis while continuing to go after SLE.
Editor’s Note: This story was updated at 1:45 am on Nov. 15 to add and clarify information about the ICANS adverse event.