Cabaletta Bio has cleared a significant regulatory milestone to advance its novel cell therapy approach for multiple sclerosis (MS), as the company moves forward with its Phase 1/2 clinical trial following FDA review completion.
The investigational therapy, resecabtagene autoleucel (rese-cel), represents a pioneering approach in autoimmune disease treatment, leveraging CAR T-cell technology traditionally associated with cancer therapy. This development marks a potential paradigm shift in MS treatment strategy.
Innovative Mechanism of Action
Rese-cel operates through a sophisticated mechanism targeting CD19, a protein abundantly expressed on B-cells. The therapy involves collecting a patient's T-cells and engineering them to recognize and eliminate B-cells, which play a crucial role in MS pathology by driving inflammatory attacks on the brain and spinal cord.
"We look forward to building on our momentum as we move closer to realizing our vision of launching the first targeted curative cell therapy designed specifically for patients with autoimmune disease," stated Steven Nichtberger, MD, CEO of Cabaletta Bio.
RESET-MS Trial Design and Patient Criteria
The RESET-MS trial establishes strict eligibility criteria to ensure appropriate patient selection. For relapsing MS patients, qualification requires:
- At least one relapse in the previous two years
- Minimum six months of high-efficacy treatment
Progressive MS participants must demonstrate:
- Objective evidence of worsening disability within the past year
- Six months minimum of standard-of-care therapy
The trial protocol excludes patients with a history of seizures or progressive multifocal leukoencephalopathy. Additionally, participants must not have received B-cell-depleting therapies such as Briumvi, Kesimpta, or Ocrevus for approximately 20 weeks prior to enrollment.
Treatment Protocol
The therapeutic process involves a carefully planned sequence:
- Administration of preconditioning chemotherapy using fludarabine and cyclophosphamide
- Delivery of a single weight-based rese-cel infusion
This approach aims to reset the immune system by temporarily depleting CD19-positive cells, potentially leading to sustained clinical improvement. The FDA has granted rese-cel fast track designation, acknowledging its potential significance in MS treatment.
Clinical Implications
The development of rese-cel represents a significant advancement in MS treatment approaches, potentially offering a more definitive solution compared to current maintenance therapies. If successful, this could establish a new treatment paradigm for autoimmune diseases, moving from chronic management to potential cure-oriented strategies.
