Patient suffers side effect in Cabaletta autoimmune CAR-T trial, but analysts unfazed

Title

Patient Experiences Side Effect in Cabaletta Bio's Autoimmune CAR-T Trial; Analysts Maintain Optimism

Keywords

Cabaletta Bio, autoimmune diseases, CAR-T therapy, rese-cel, immune effector cell-associated neurotoxicity syndrome (ICANS), RESET clinical trials, side effects, immunology, systemic sclerosis (SSc), systemic lupus erythematosus (SLE), myositis

Key Facts

- Clinical Trial Information:

• Cabaletta Bio is developing CAR-T therapy, resecabtagene autoleucel (rese-cel), for autoimmune diseases under the RESET clinical trial program15.
• Trials target diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myositis, generalized myasthenia gravis, multiple sclerosis, and pemphigus vulgaris1.

- Reported Adverse Event:

• A patient with SSc experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), a known CAR-T therapy side effect1.
• Symptoms included confusion but resolved quickly with dexamethasone treatment, with no long-term impacts reported1.

- Cause and Protocol Adjustment:

• The adverse event was linked to a protocol violation (fever unreported before infusion). Cabaletta updated the protocol to improve patient monitoring before infusion18.

- Analyst and Investor Reaction:

• Analysts expressed optimism over the therapy's potential, emphasizing the importance of managing peri-infusion risks1.
• Despite the positive long-term outlook, Cabaletta's stock dropped 15% after the announcement1.

- Efficacy Data:

• Preliminary data suggests rese-cel provides signs of efficacy across multiple autoimmune diseases, including remission in some SLE patients off immunosuppressants56.
• Phase 1/2 data indicates a promising safety profile in early trials, with most patients experiencing mild or no serious side effects such as cytokine release syndrome (CRS) or ICANS5.

- CAR-T Therapy in Autoimmune Diseases:

• Originally developed for cancer, CAR-T therapy modifies T cells to target and reset the immune system. It holds promise for treating refractory autoimmune conditions10.
• While serious side effects like ICANS and CRS are concerns, they appear to be less frequent in autoimmune trials compared to oncology applications10.

- Next Steps:

• Cabaletta plans to discuss trial designs with the FDA for potential registrational studies in 2025, aiming to offer a first-in-class autoimmune CAR-T therapy56.

Sources:

1. https://www.fiercebiotech.com/biotech/patient-suffers-side-effect-cabaletta-autoimmune-car-t-trial-analysts-unphased

5. https://www.fiercebiotech.com/biotech/cabalettas-car-t-shows-robust-benefit-lupus-patients-teeing-registrational-trial-plans

6. https://www.cabalettabio.com/investors/news-events/press-releases/detail/125/update---cabaletta-bio-announces-updated-clinical-data

8. https://www.cabalettabio.com/investors/news-events/press-releases/detail/119/cabaletta-bio-presents-positive-clinical-safety-and

10. https://www.science.org/content/article/breakthrough-cancer-immunotherapy-now-taking-aim-autoimmune-disease