Tiziana Life Sciences’ intranasal foralumab has shown potential in treating nonactive secondary progressive multiple sclerosis through innovative immune modulation.
Gabriele Cerrone
According to a new announcement, the FDA has granted fast track designation to Tiziana Life Sciences’ intranasal foralumab, a fully human anti-CD3 monoclonal antibody, for the treatment of nonactive secondary progressive multiple sclerosis (na-SPMS).1 Intranasal foralumab is designed to bind to T cell receptors and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets.
"We are thrilled to receive fast track designation from the FDA for intranasal foralumab for the treatment of multiple sclerosis," Gabriele Cerrone, chairman, acting CEO and founder at Tiziana Life Sciences, said in a statement.1 "This designation underscores the potential of foralumab to address critical unmet needs in the treatment of neurodegenerative diseases. We are committed to advancing this promising therapy as quickly as possible to benefit patients."
As of July 2024, 10 patients with na-SPMS were dosed in an open-label intermediate sized Expanded Access (EA) program, all of whom either improved or showed stability of disease across 6 months. Recently, the FDA allowed an additional 20 patients to be enrolled in this EA program, increasing the cohort to a total of 30 patients.2 The company noted that patients with na-SPMS who were not eligible for the phase 2a trial (NCT06292923) assessing the treatment, initiated in November 2023, were considered for this EA program.
"Receiving fast track designation is a testament to the innovative approach we are taking with foralumab," William Clementi, PharmD, FCP, chief development officer at Tiziana Life Sciences, said in a statement.1 "We believe that the intranasal delivery method offers a novel way to effectively target neuroinflammation, and we look forward to working closely with the FDA to bring this therapy to patients in need."
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At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, significant findings from the open-label EA program revealed that foralumab treatment resulted in damped microglial activation and clinical stability in patients with na-SPMS who had progression independent of relapses (PIRA).3 Investigators are planning a double-blind, placebo-controlled, dose-ranging study of the agent in this population using (F-18)PBR06-PET, the main tool used to measure microglial activation, as a primary end point.
At both the 3-and 6-month time points, 5 of 6 foralumab-treated patients (83%; 95% CI, 44%-97%) demonstrated a qualitative reduction in (F-18)PBR06-PET in multiple brain regions. Patients in the small-scale study also had stable Expanded Disability Status Scale (EDSS) scores and improvements in Modified Fatigue Impact Scale (MFIS) as a result of foralumab treatment. Following promising preclinical studies, lead author Tarun Singhal, MD, MBBS, and colleagues, aimed to assess the effect of nasal foralumab in patients with na-SPMS with PIRA.
In the study, a voxel-by-voxel z-score mapping approach was used and sum of z-scores in voxels with z-values of more than 2 were calculated. In addition to the 6 patients, the study also included 2 patients with na-SPMS with PIRA who underwent a test and a retest (F-18)PBR06-PET scan. In the foralumab-treated group, white matter z-scores were reduced by 26%-36% at 3 and 6 months, which was at least 4-5-times higher compared to the 6% variability observed in the test-retest group (PET effect size estimate at 3 months, 1.4).3
Singhal, director of the PET Imaging Program in Neurologic Diseases at Brigham and Women’s Hospital, sat down with NeurologyLive® at the meeting to further discuss the significance of PIRA in the progression of MS. He also spoke about how PET imaging may aid in identifying hidden inflammation in the brain. Singhal, who also serves as an associate professor of neurology at Harvard Medical School, also explained the implications of the findings from the recent study assessing foralumab as a potential treatment for patients with na-SPMS.
