In an open-label study of 10 patients with non-active secondary progressive multiple sclerosis, intranasal foralumab showed no serious or severe treatment-related adverse events, stabilization of EDSS in all patients, and EDSS improvement in three of four patients treated for 12 months. Six of ten reported fatigue improvements on MFIS. MRI showed no new T2 lesions. TSPO-PET showed significant reductions in microglial activation at 3 and 6 months (p<0.05), and single-cell RNA sequencing revealed sustained increases in Tregs and TGFβ expression, consistent with a regulatory immune shift. The core development is the publication of these findings in Neurology Neuroimmunology & Neuroinflammation, elevating a previously disclosed dataset into the peer-reviewed domain. The study is notable for integrating TSPO-PET, proteomics, and clinical outcomes to interrogate progression independent of relapse activity in na-SPMS. Tiziana is already running a randomized, double-blind, placebo-controlled Phase 2 trial in this population, with top-line data expected in the first half of 2026. The company also cites an expanded access cohort in which 14 patients have shown stability or improvement within six months, adding real-world texture to the signal, albeit with similar open-label limitations. Strategically, the publication serves as an external validation step ahead of a pivotal proof-of-concept readout and aims to position foralumab as a mechanism-differentiated option in a segment with limited therapies and diminishing returns from chronic B-cell suppression. The intranasal, mucosal tolerance approach targets microglial-driven neuroinflammation without broad systemic immunosuppression, which is a deliberate contrast to existing MS backbones. The inclusion of TSPO-PET and single-cell profiling is a biomarker-forward bet: it could de-risk the mechanism with regulators and KOLs, but also raises the bar for reproducibility and standardization in larger, multicenter settings. For sites and CROs, the operational footprint is non-trivial. TSPO-PET requires tracer availability, harmonized acquisition protocols, and centralized reads to manage inter-site variability, which may constrain the site network to centers with advanced neuroimaging infrastructure. The omics work introduces additional complexity in sample handling and analytics. On the upside, self-administered intranasal dosing can reduce visit burden and enable hybrid designs, potentially easing retention in a notoriously slow-recruiting na-SPMS population. Imaging CROs and biomarker vendors will see opportunities in PET standardization, quantitative analytics, and immune profiling panels if this modality set becomes core to the program. Regulators are likely to view TSPO-PET as supportive pharmacodynamic evidence rather than a registrational endpoint; the Phase 2 design will need to anchor on clinically meaningful measures of progression, such as EDSS and functional composites aligned to PIRA. Payers will focus on durability and functional impact beyond imaging, and on comparative context relative to anti-CD20-treated patients who still progress despite the absence of overt inflammatory activity. Near term, the watch items are Phase 2 endpoint selection, target effect size, and variance assumptions in a heterogeneous na-SPMS population, and the durability of the EDSS signal to 12 months. Standardization of TSPO-PET across sites and assay reproducibility for immune biomarkers will be critical for credibility. Longer term, the program’s risk hinges on translating a small open-label signal into a controlled setting, establishing chronic safety of intranasal anti-CD3, and scaling CMC and device logistics for a nasal biologic. If the randomized data corroborate both clinical stabilization and mechanistic readouts, the path opens to expedited regulatory dialogues; if not, the reliance on advanced imaging and biomarker narratives could be viewed as overfit to early-stage biology rather than translatable clinical benefit.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
