FDA clears way for Phase 1/2 trial of CAR T-cell therapy in SSc patients
CABA-201 to be tested in those with severe skin or internal organ manifestations
The U.S. Food and Drug Administration (FDA) has cleared Cabaletta Bio’s request to begin clinical testing of CABA-201, a cell therapy for adults with hard-to-treat systemic sclerosis (SSc).
Cabaletta now plans to launch a Phase 1/2 clinical trial, enrolling SSc patients with severe skin manifestations or organ involvement despite treatment with immune-suppressing medications.
“We believe CABA-201 has the potential to slow or halt the progression of this autoimmune disease, thereby providing an important treatment option for these patients who currently have very few available treatments,” Steven Nichtberger, MD, Cabaletta’s CEO and co-founder, said in a company press release.
Scleroderma clinical trial will be third patient test of CABA-201
An autoimmune disease, SSc, or scleroderma, is marked by the accumulation of scar tissue in the skin and potentially in internal organs such as the heart, lungs, kidneys, and digestive tract. Current disease treatments include corticosteroids and other therapies that suppress the immune system or block excess scar formation.
Autoimmune attacks in SSc are driven by hyperactive B-cells, the immune cells that produce antibodies. Overactive B-cells produce antibodies that damage and cause inflammation in tissues.
CABA-201 is a CAR T-cell therapy that targets CD19, a protein found on B-cells involved in various autoimmune diseases and blood cancers.
The cell therapy consists of modifying a patient’s own immune T-cells with a chimeric antigen receptor, called CAR, which is designed to recognize and eliminate disease-driving B-cells. It also harbors 4-1BB (also called CD137), a protein involved in T-cell survival and activation.
Developed using Cabaletta’s CABA platform, the therapy is similar to an anti-CD19-CAR T therapy that successfully treated a 60-year-old man with severe SSc-related skin, lung, and heart involvement.
In this patient, the CAR T-cell therapy was well tolerated, with only a mild fever for less than 24 hours and no signs of ICANS, or immune effector cell-associated neurotoxicity syndrome. This neurological complication, which can lead to confusion, attention deficits, and word finding difficulties, has been seen in other patients on CAR-T cell therapy.
The Phase 1/2 clinical trial of CABA-201 will be an open-label study, meaning there’s no placebo arm. It plans to recruit two groups of six SSc patients, ages 18-70: one with severe skin manifestations and the other with organ involvement (heart, lungs, kidneys), regardless of skin manifestations.
The study will evaluate CABA-201’s ability to eliminate disease-causing B-cells throughout the body, with the goal of slowing or halting active inflammatory disease progression.
Recently, the FDA gave the green light to the company’s requests to test its CAR T-cell therapy in people with other autoimmune diseases, such as lupus and myositis (muscle inflammation). According to Cabaletta, Phase 1/2 trials of CABA-201 in lupus and myositis are ongoing, following the same dosing regimen to be used in SSc patients, with three-month data expected early in 2024.
“As we remain on track to deliver three-month clinical data from the initial patients treated with CABA-201 by the first half of 2024,” Nichtberger said, “the clearance of our third … application for CABA-201 within the past 6 months demonstrates our relentless focus on developing CABA-201 for a broad portfolio of potential indications in patients with autoimmune diseases.”
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