CABA-201 gets FDA orphan drug status as scleroderma treatment

CAR T-cell therapy for SSc designed to eliminate hyperactive B-cells by Steve Bryson, PhD | March 26, 2024

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Cabaletta Bio’s cell therapy CABA-201 as a treatment for adults with hard-to-treat systemic sclerosis (SSc), or scleroderma.
Orphan drug designation is intended to support the accelerated development of investigational treatments for rare diseases, defined as those affecting fewer than 200,000 people in the U.S. The designation provides Cabaletta with regulatory support, financial incentives, and seven years of market exclusivity if CABA-201 is approved.
“Orphan drug designation is an important recognition for investigational therapies for rare diseases, and provides us with potentially valuable benefits as we develop CABA-201 for patients with systemic sclerosis,” David J. Chang, MD, chief medical officer of Cabaletta, said in a company press release.
CABA-201 received FDA fast-track designation to reduce SSc-associated organ dysfunction in January. That status is designed to speed the development of therapies that address unmet medical needs for serious conditions.
The FDA in October cleared Cabaletta’s request to launch a Phase 1/2 clinical trial, RESET-SSc (NCT06328777), to evaluate CABA-201 in 12 adults, ages 18-70. Location information on the study, expected to start in June, is not yet available.

Scleroderma treatment options have ‘only modest’ effects“
Patients diagnosed with systemic sclerosis, a rare and life-threatening chronic autoimmune disease characterized by progressive skin and internal organ fibrosis [scarring], face limited treatment options as current therapies provide only modest effects and focus on treating the complications associated with the disease,” Chang said. “With an average patient survival of 12 years following diagnosis, there is a significant unmet need for new treatment options that focus on eliminating the root cause of the disease to prevent further organ damage for patients.”
Hyperactive B-cells, the immune cells that produce antibodies, drive the autoimmune attacks in SSc. When overactive, B-cells produce antibodies that cause inflammation and damage in healthy tissues.
Developed using Cabaletta’s CABA platform, CABA-201 is a CAR T-cell therapy designed to eliminate B-cells. CAR T-cell therapies use the patient’s own immune T-cells to mount an attack against specific targets.
CABA-201 treatment involves the collection of a patient’s immune T-cells and their modification in the lab to carry a chimeric antigen receptor (CAR) that targets CD19, a protein found on B-cells involved in various autoimmune diseases. The CAR also contains a protein domain involved in T-cell survival and activation called 4-1BB.
The modified T-cells are then infused back into the patient, with the aim of depleting B-cells for durable disease remission.

In a previous study, a similar anti-CD19-CAR T therapy was shown to safely and effectively treat a 60-year-old man with severe, treatment-resistant SSc and heart, lung, and skin involvement.
“Based on the role of B-cells and the recently published academic clinical data with CD19-CAR T therapy in systemic sclerosis, we believe CABA-201 may transform the treatment for systemic sclerosis,” Chang said.
The RESET-SSc study plans to enroll two groups of six patients, one group with severe skin involvement and the other with heart, lung, and/or kidney involvement, with or without skin manifestations. The trial has no placebo group, and all participants will receive treatment.
Following a one-time infusion, CABA-201’s safety and tolerability will be assessed for 28 days after treatment as the main study goal.
Secondary outcomes, measured for as long as three years, include the incidence and severity of side effects, and the therapy’s pharmacological properties, including its effects on B-cell levels.
Researchers will measure the proportion of patients with significant reductions in disease severity as assessed by the Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score.
CABA-201 also received FDA fast-track designation to treat lupus, another autoimmune condition, and dermatomyositis, a rare disorder characterized by muscle weakness and skin rash.