TSPO-PET imaging in an Alzheimer’s patient already on lecanemab showed persistent, widespread microglial activation, underscoring residual neuroinflammation despite amyloid clearance. Against that backdrop, Tiziana Life Sciences has begun enrollment in a Phase 2 randomized, placebo-controlled trial of intranasal foralumab in early Alzheimer’s disease, with first dosing expected next week.
The study will test foralumab both as monotherapy and as an add-on to anti-amyloid therapy (lecanemab or donanemab). Baseline clinical assessments, cognitive testing, TSPO-PET imaging, and fluid biomarkers have been completed in initial participants. Key endpoints include changes in neuroinflammation by TSPO-PET, cognition, and amyloid/tau-related biomarkers. The company positions intranasal foralumab, a fully human anti-CD3 monoclonal antibody designed to induce regulatory T cells, as a way to attenuate microglial activation that appears to persist after amyloid reduction. Tiziana is also leaning on prior neuroinflammation signals from multiple sclerosis to support the mechanistic rationale as it moves into Alzheimer’s.
Strategically, this is an add-on and differentiation play in the post-amyloid era. With anti-amyloid agents setting a new baseline but leaving room on clinical outcomes, sponsors are targeting inflammation, tau, and synaptic health to extend benefit. Tiziana’s bet is that immunomodulation via the intranasal route can deliver brain-relevant effects with manageable safety and operational burden. The combination arm pragmatically aligns the program with current standard-of-care trajectories, while the monotherapy arm tests whether dampening neuroinflammation alone can slow decline—an approach that, if credible, could broaden use beyond patients eligible for or willing to take amyloid therapies.
For sites and CROs, the operational signal is clear: this is an imaging-heavy protocol requiring TSPO-PET infrastructure, radiochemistry logistics, and genotype-aware tracer selection due to known TSPO affinity polymorphisms that affect quantification. Centers will need to layer TSPO-PET workflows on top of the MRI monitoring already required for ARIA in anti-amyloid-treated patients, increasing scheduling complexity and imaging core lab reliance. Combination arms will require tight coordination with infusion centers and careful safety surveillance to rule out interaction effects, even if mechanisms are orthogonal. Sites recruiting patients already on lecanemab or donanemab will also need clear rules for stabilization, blinding, and endpoint timing to preserve interpretability.
Regulatory and payer relevance will hinge on more than PET changes. TSPO-PET can anchor pharmacodynamic credibility, but regulators will expect concordant effects on cognition and function, and payers will scrutinize additive benefit over anti-amyloid alone. The field’s ongoing debate over TSPO specificity and intersubject variability raises a bar for robust imaging analytics and pre-specified handling of low- and high-affinity binders. If the study shows reduced microglial signal without clinical divergence, the path to a broadly usable label will remain narrow.
Near term, watch for initial dosing and clarity on sample size, duration, and interim PD readouts—particularly the timing of TSPO-PET assessments at three to six months and any signal on ARIA rates in combination arms. The key risk is over-indexing on an imaging surrogate that fails to translate to clinical outcomes; the key upside is a demonstrable cognitive benefit that validates neuroinflammation as a modifiable driver in early Alzheimer’s. If a coherent efficacy package emerges, the next questions will be durability, adherence to chronic intranasal dosing, and the feasibility of integrating an immunomodulator into already resource-intensive Alzheimer’s care pathways.
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.
