EDSS Score Drop of 1 Point Seen in 2nd SPMS Patient on Foralumab

A second person with non-active secondary progressive multiple sclerosis (SPMS) treated with foralumab nasal spray in a single-patient access program is continuing to show improvements 11 months after starting the therapy, according to an update from foralumab’s developer, Tiziana Life Sciences.

The patient, dubbed EA2, experienced a one-point drop — indicating lesser disability — on the Expanded Disability Status Scale (EDSS) score as of December. Treatment began in January 2022.

Five other SPMS patients with non-active disease currently are being dosed with intranasal foralumab under expanded access programs at the Brigham and Women’s Hospital (BWH) in Boston.

Tiziana previously announced plans to launch a proof-of-concept Phase 2 trial evaluating foralumab in non-active SPMS patients this year, pending feedback from the U.S. Food and Drug Administration (FDA) on the trial’s design.

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“The sustained improvement in EDSS score starting at 6 months and further improving after 11 months on foralumab treatment in patient EA2 is impressive and warrants further study in a Phase 2 trial,” Tanuja Chitnis, MD, a neurology professor and principal investigator of the study at BWH, said in a company press release.

Foralumab is an antibody-based treatment designed to target the CD3 protein found on the surface of T-cells, a type of immune cell implicated in the inflammation that drives MS and other neurodegenerative diseases.

Preclinical data have shown that foralumab works to lessen the activity of T-cells, while activating a set of immunosuppressive cells called regulatory T-cells. The regulatory T-cells travel to the brain and inhibit the activation of microglia, the brain’s resident immune cells that are known to drive inflammation in neurodegenerative diseases.

Tiziana expects the treatment can benefit people with non-active SPMS, characterized by disability progression in the absence of relapses. SPMS is “an advanced stage of multiple sclerosis with few treatment options and creates a severe burden on patients,” said Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at BWH and chairman of Tiziana’s scientific advisory board.

Clinical testing of foralumab nasal spray in this patient group began with two single-patient access programs, which are currently ongoing at BWH. Patients are receiving a 50 microgram dose of the spray into each nostril in three-week cycles — three doses per week for two weeks, followed by a week of rest.

Data from the first patient showed the therapy was well-tolerated, and led to clinical improvements after six months. The benefits were accompanied by a suppression of microglial activity in the brain, as observed on PET scans.

This prompted the FDA to clear the first patient to continue receiving foralumab for another six months, and enabled a second SPMS patient to start treatment.

The second patient, EA2, had experienced significant disability progression since an SPMS diagnosis, going from an EDSS score of 3.5 in 2018, representing moderate disability, to 6.0 in 2021, meaning the patient required a cane to walk 100 meters. This progression occurred despite treatment with Ocrevus (ocrelizumab).

‘Sustained’ drop in EDSS score with non-active SPMS is ‘noteworthy’

The patient was enrolled in the expanded access program in January 2022. After three months of foralumab nasal spray treatment, neurological and walking improvements were reported, accompanied by a 10% to 30% reduction in microglial activation on PET scans.

As of a September report, those improvements were sustained for six months, with the being patient able to walk 100 meters without a cane, corresponding to an EDSS score reduction from 6 to 5.5.

In the latest update, Tiziana reports that as of December — 11 months after starting treatment — patient EA2 was able to walk 200 meters without a cane, corresponding to a drop in EDSS score from 5.5 to 5 — an overall drop of one point since starting treatment.

The EDSS pyramidal score, which evaluates muscle weakness and moving difficulties, has remained stable for the duration of treatment.

“Patients with non-active SPMS normally do not improve by a sustained reduction of 1.0 on their EDSS score, so this finding is noteworthy,” Chitnis said.

A preliminary reading of the patient’s 11-month PET scan also demonstrated a reduction in microglial activation relative to levels prior to starting treatment.

Early data from these first two patients led the FDA to clear an intermediate-size expanded access program for up to eight patients. Four other SPMS patients are enrolled in that program, allowing treatment with foralumab nasal spray at a 50 microgram dose. Additional data from all six patients are expected later this year, Tiziana noted in November.

“EA2’s clinical improvement justifies Tiziana’s decision to make intranasal foralumab for non-active SPMS our top priority,” said Gabriele Cerrone, executive chairman and interim CEO of Tiziana.

The company is also developing foralumab for other neurological diseases marked by microglial activation, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.