Phase 1/2 trial will test cell therapy rese-cel in relapsing, progressive MS
RESET-MS will enroll adults, ages 18-60, to test CAR T-cell therapy
Cabaletta Bio is getting set to launch a clinical trial testing its cell therapy resecabtagene autoleucel (rese-cel) in people with relapsing and progressive forms of multiple sclerosis (MS).
The company sought permission last year from the U.S. Food and Drug Administration (FDA) to start the study. Once such an application is submitted, the FDA has 30 days to review it for any safety issues. That 30-day window has elapsed, meaning Cabaletta can proceed with its study.
“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,” Steven Nichtberger, MD, CEO of Cabaletta, said in a company press release.
In MS, an inflammatory attack damages healthy parts of the brain and spinal cord, with B-cells, the immune cells responsible for making antibodies, playing a prominent role in driving the disease. Rese-cel, previously called CABA-201, is a CAR T-cell therapy that’s designed to treat MS by depleting B-cells.
In CAR T-cell therapies, immune cells called T-cells are collected from a patient, then engineered to equip them with a man-made receptor that targets a specific protein. In rese-cel, the T-cells are equipped with a receptor that targets CD19, a protein found at high levels on the surface of B-cells.
The engineered cells are then infused back into the patient’s bloodstream so they can attack and destroy B-cells. By temporarily and completely depleting all CD19-positive cells, the therapy could potentially reset the immune system, leading to strong and durable clinical responses, according to the company.
Rese-cel has received fast track status from the FDA as a potential MS treatment. The designation is aimed speeding up the development and review of potentially important new therapies.
Testing cell therapy in RESET-MS study
The upcoming Phase 1/2 clinical trial, dubbed RESET-MS, will enroll adults, ages 18-60, who have either relapsing or progressive forms of MS.
To be eligible, patients with relapsing MS must have had at least one relapse in the previous two years and been on high-efficacy treatment for at least six months. Progressive MS patients must show objective evidence of worsening disability in the year before and have been on standard-of-care therapy for at least six months.
Patients who have a history of seizures or progressive multifocal leukoencephalopathy, a potentially life-threatening infection that can occur in people on certain MS therapies, aren’t eligible to participate. Patients also cannot have taken MS treatments that work by depleting B-cells for about 20 weeks before entering the study. B-cell-depleting MS therapies include anti-CD20 antibodies like Briumvi (ublituximab), Kesimpta (ofatumumab), and Ocrevus (ocrelizumab).
All the trial’s participants will first be given the chemotherapy drugs fludarabine and cyclophosphamide as part of a preconditioning regimen to destroy their existing immune cells and make room for the therapeutic cells. After the preconditioning, they will all be given a one-time, weight-based infusion of rese-cel.
Caballeta didn’t specify when the trial might begin enrollment or where it will take place. The company is also developing rese-cel for several other autoimmune conditions where B-cells play a major role, including myasthenia gravis, lupus, and systemic sclerosis. Phase 1/2 trials are already ongoing for those indications.
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