FDA gives go-ahead for trial testing CAR T-cell therapy for progressive MS

The U.S. Food and Drug Administration (FDA) has given Abelzeta Pharma the go-ahead to launch an early-stage clinical trial to test its CAR T-cell therapy candidate for multiple sclerosis (MS) in people with hard-to-treat, progressive forms of the disease.

According to Abelzeta, the study’s first part will enroll as many as two dozen people with progressive MS to determine the recommended dosage for the experimental treatment, dubbed C-CAR168. That dose will then be used throughout the trial, which will recruit participants whose MS has not responded to standard therapy, the developer stated in a company press release announcing the regulatory clearance.

“Progressive multiple sclerosis can cause significant and irreversible neurological disability, and there remains a considerable unmet medical need for therapies capable of addressing the underlying immune dysfunction driving disease progression,” said Tony (Bizuo) Liu, chairman and CEO of Abelzeta. “The FDA clearance of this Phase 1b/2 study represents another important step in realizing the potential of C-CAR168 across refractory [treatment-resistant] chronic autoimmune diseases.”

Abelzeta stated that the trial will be conducted at multiple study sites, but did not provide a timeline.

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MS is an autoimmune disease that causes damage to the brain and spinal cord, resulting in symptoms that can range from movement problems and vision issues to cognitive impairment.

Progressive MS — which encompasses both primary progressive MS (PPMS) and secondary progressive MS (SPMS) — is defined by symptoms that gradually worsen over time, irrespective of the occurrence of disease flares, or periods of sudden symptom worsening.

Treatment options for progressive forms of MS are limited compared with the strategies available to those with relapsing forms of the disease, which are marked by flares.

CAR T-cell therapy showed benefit in earlier trial

C-CAR168 is an autologous CAR T-cell therapy, a type of treatment that uses a patient’s own immune cells. First, an individual’s T-cells — immune cells capable of killing other cells — are collected. The T-cells are then engineered in a lab to equip them with a chimeric antigen receptor (CAR), a human-made protein that directs the T-cells to attack a specific target. The modified cells are then infused back into the body to go after the target.

The CAR used in C-CAR168 specifically targets two proteins: CD20 and BCMA. Both are produced by B-cells, a type of inflammatory immune cell thought to have a key role in driving MS. By depleting B-cells, the therapy aims to reduce the inflammation that drives MS.

Abelzeta is developing C-CAR168 as a potential treatment for progressive MS and other immune disorders, such as lupus and systemic sclerosis, that are driven by B-cells.

An ongoing first-in-human trial (NCT06249438) is exploring C-CAR168’s use in various hard-to-treat autoimmune disorders, including so-called refractory MS. In that study, according to Abelzeta, the therapy candidate has shown promise in participants with progressive MS.

Based on updated preliminary efficacy data [from an earlier trial] … we remain cautiously optimistic that the deep immune-cell depletion and reset enabled by C-CAR168 can provide meaningful and durable benefit to [progressive MS] patients.

Effectiveness data from one of the two SPMS patients, previously presented, showed less MRI lesion burden, improved walking and cognitive function, and reduced overall disability after six months on the therapy. Updated data from both patients appear to continue to support C-CAR168’s therapeutic potential, according to Abelzeta.

“Based on updated preliminary efficacy data, including early and sustained [disability lessening] and functional improvement observed in two secondary progressive multiple sclerosis (SPMS) patients, … we remain cautiously optimistic that the deep immune-cell depletion and reset enabled by C-CAR168 can provide meaningful and durable benefit to these patients,” Liu said. Liu noted that one patient had active disease while the other’s was non-active, and one was followed for more than one year.

According to the developer, the upcoming multicenter Phase 1b/2 trial will test C-CAR168 in people with SPMS or PPMS that has not responded adequately to standard treatment. In the trial’s Phase 1b portion, between six and 24 people with SPMS or PPMS will be given C-CAR168 at various doses, with the main goal of determining the best dose for testing in the Phase 2 portion.

The Phase 2 part of the study will enroll approximately 95 people across two groups: one comprising active SPMS patients with relapses or new MRI lesions, and the other involving individuals with PPMS or nonactive SPMS.

Abelzeta did not provide further details about the study’s design, locations, or its expected timeline.