50 μg foralumab met the neuroinflammation endpoint in non-active secondary progressive MS
Tiziana Life Sciences’ intranasal foralumab met a key phase 2a goal in non-active secondary progressive multiple sclerosis, but the signal was dose-sensitive. In the 48-patient Inform-MS study, the lower 50 μg dose produced a statistically significant reduction in neuroinflammation on PET imaging, while the 100 μg dose did not clear that bar.
The imaging result matters because progressive MS often advances through a slower, smoldering inflammatory process rather than the abrupt relapses seen earlier in the disease course. In that setting, a therapy that can dampen central nervous system inflammation without adding meaningful toxicity has a plausible therapeutic role, especially when no FDA-approved treatment is specifically indicated for non-active secondary progressive MS.
PET imaging separated the two dose cohorts
Investigators randomized participants to 50 μg intranasal foralumab, 100 μg intranasal foralumab, or placebo over 12 weeks. PET scans in evaluable patients showed a 0.0231 reduction in the white-matter/global-brain SUVR ratio in the 50 μg group versus placebo. Tiziana described the difference as statistically significant and counted it as one of the study’s dual primary endpoints.
The higher 100 μg dose, by contrast, failed to demonstrate a statistically significant change in SUVR during PET scanning. In practical terms, the study did not show a simple dose-response curve in which more drug produced a larger biological effect. For an intranasal immunotherapy aimed at central neuroinflammation, that pattern raises a pharmacologic question: the lower dose may have landed in a more favorable immunomodulatory range, while the higher dose may have offered no added benefit for the inflammatory pathway being measured.
The divergence was abrupt. One dose moved the imaging biomarker, the other did not.
Safety held across all 48 enrolled patients
The safety endpoint was more straightforward. All 48 participants completed treatment, and no serious adverse events were linked to foralumab. Across both active-dose groups, 76.7% of patients experienced treatment-emergent adverse events, compared with 83.3% in the placebo group.
Headache, fall, nasal congestion, and rhinorrhea were the most common treatment-emergent adverse events among patients receiving foralumab. The nasal route is clinically relevant here: local irritation and upper-airway symptoms are predictable with intranasal delivery, but the absence of serious drug-related events helps support the tolerability of the approach in a population already carrying substantial neurologic disability.
For progressive MS, safety is not a secondary concern. Many patients are older, functionally limited, and living with chronic symptoms that can be worsened by systemic immunosuppression. A treatment with a clean serious-adverse-event profile in a small mid-stage trial will not settle the question of long-term risk, but it does keep the door open for further development.
Fatigue improved even when disability did not
Fatigue moved in the right direction. On the Modified Fatigue Impact Scale, the 50 μg cohort recorded a 6.17-point decrease, and the 100 μg group showed a 7.18-point drop. Placebo produced no significant change, allowing Tiziana to describe the fatigue result as statistically significant for the drug.
Fatigue is one of the most disabling symptoms in progressive MS, often out of proportion to what a standard neurologic exam captures. A therapy that improves fatigue without parallel gains on a disability scale can still be clinically meaningful, because daily functioning in this disease is shaped by energy, stamina, and cognitive reserve as much as by walking scores alone. Even so, the fatigue signal will need confirmation in a larger study with careful attention to durability and measurement bias.
The Expanded Disability Status Scale did not show a benefit. In a disease defined by cumulative neurologic decline, the lack of EDSS separation tempers enthusiasm and keeps the interpretation grounded: the study suggests biological activity and symptomatic improvement, but not yet a proven disability-modifying effect.
Why the result still leaves an open translational question
Foralumab is an anti-CD3 monoclonal antibody delivered intranasally, a strategy designed to modulate immune activity through mucosal exposure rather than broad systemic suppression. That mechanism makes conceptual sense in MS, where immune activation drives neuroaxonal injury and compartmentalized inflammation can persist even when overt relapses disappear. If the lower dose truly suppresses neuroinflammatory activity more effectively than the higher dose, the result may reflect immune signaling that depends on precise exposure rather than simple dose escalation.
The trial’s readout also fits the broader clinical challenge in non-active secondary progressive MS. Disability and fatigue worsen over time, yet the therapeutic toolbox remains limited, and conventional relapse-focused metrics often fail to capture the biology of progression. PET imaging offered a closer look at that biology, while MFIS gave the study a symptomatic lens. EDSS, by comparison, did not move.
That split is informative. It suggests that a treatment can influence inflammatory biomarkers and patient-reported fatigue without immediately changing the harder endpoint of disability progression.
Tiziana is preparing an FDA discussion and a broader development strategy
Tiziana said it plans to engage with the FDA to discuss the findings and the potential path forward for intranasal foralumab in na-SPMS. The company framed the disease area as one with a significant unmet need, particularly around progressive disability and fatigue, which is consistent with the absence of FDA-approved therapies specifically indicated for that population.
Chief executive Ivor Elrifi said the statistically significant and clinically significant improvements from baseline in MFIS at both doses strengthened the company’s conviction in the program. He also pointed to accumulated real-world evidence from an expanded access program in na-SPMS, plus emerging data in Alzheimer’s disease, amyotrophic lateral sclerosis, and multiple system atrophy, as the company advances foralumab to the next stage of development.
That broader pipeline context matters because Tiziana has narrowed its focus on foralumab after planning to spin out its interleukin-6 receptor candidate into a separate company. The present dataset now becomes a central piece of the company’s case for continued development.
Still, the study remains small, short, and selective. The 100 μg dose did not reproduce the imaging result, EDSS did not improve, and the 12-week window does not answer whether the biomarker and fatigue gains can hold over longer treatment or translate into slower disability accumulation. Those are the next questions FDA discussions will have to confront.