Nasal Foralumab Shows Significant Imaging Signal at 50 Micrograms in Multiple Sclerosis Study
Key Facts
Tiziana Life Sciences announced on November 2 that the randomized, double-blind, placebo-controlled INFORM-MS trial met its two primary endpoints in patients with non-active secondary progressive multiple sclerosis. The company said the 50-microgram dose of nasal foralumab reduced microglial activation on PET imaging versus placebo after 12 weeks, with a p-value of 0.0168. The first endpoint was to detect this imaging reduction, while the second was safety and tolerability. The reported result therefore centers on an imaging biomarker signal and the tolerability profile during the study period. The company stressed that the result does not establish a definitive clinical improvement in disease symptoms.
The study was conducted at 8 U.S. clinical sites, with participants randomized to placebo and two foralumab groups receiving 50 and 100 micrograms. The placebo group included 18 participants, compared with 19 in the lower-dose group and 11 in the higher-dose group. Treatment lasted 12 weeks, across 4 consecutive cycles of 3 weeks each. This design allows the two doses to be compared with placebo over the same period, while participants and researchers remained unaware of treatment assignments during the blinded portion. The company announced that all 48 participants completed treatment.
In the statistically adjusted analysis of PET scans, the adjusted treatment difference in the white-matter SUV ratio was −0.0231, with a 95% confidence interval between −0.0416 and −0.0046. The analysis was based on evaluable scans from 40 participants, and the p-value for the difference was 0.0168. The company said the result was achieved with the 50-microgram dose after 12 weeks, consistent with its report of a statistically significant reduction in microglial activation. By contrast, PET analysis in the 100-microgram group showed no statistically significant difference; that group included 11 participants. The initial results reported by the company therefore showed different imaging signals for the two doses.
On safety, Tiziana said all 48 participants completed treatment, with no deaths or serious drug-related events, and no participants discontinued treatment because of side effects. Treatment-emergent adverse events were recorded in 15 of 18 participants in the placebo group, or 83.3%. Across both foralumab groups, the events occurred in 23 of 30 participants, or 76.7%. These figures place the reported tolerability results alongside the imaging result, with safety and tolerability forming one of the trial’s two primary endpoints. The statement did not say that this comparison establishes clinical symptom superiority over placebo.
The company nevertheless set limits on what could be inferred clinically from the study. It said the trial was not designed to establish definitive changes in measures such as fatigue, and it observed no change in the secondary EDSS measure during the 3-month treatment period. This means that meeting the imaging endpoint is not equivalent to establishing a definitive improvement in disability or symptoms over this period. The company explained that the study was not sufficiently powered to establish decisive clinical changes. Accordingly, fatigue outcomes, like the EDSS measure, remain within the limits on inference described by the company and do not replace the primary imaging endpoint.
The company said in September that participants, including those who received placebo during the blinded portion, had the option to continue treatment with foralumab in a 6-month open-label extension. The extension offers an opportunity to collect longer-term safety and efficacy data, according to the company’s announcement at the time. Following the initial results, Tiziana plans to complete the full data analysis and present detailed findings at a future scientific conference. It also said it would discuss the results and potential development path with the FDA, without specifying a timetable for these steps in the statement. TLSA shares closed at $0.67 on November 2, compared with a close of $0.8 on October 30.