Phase 2 Trial Shows IFB-088 Safe but Ineffective for Bulbar ALS When Combined with Riluzole

IFB-088 Shows Safety but Falls Short on Efficacy in Bulbar ALS Trial

InFlectis BioScience has completed a Phase 2 clinical trial of IFB-088 (icerguastat) in patients with bulbar-onset amyotrophic lateral sclerosis (ALS). The exploratory study showed that while the drug demonstrated an acceptable safety profile, it did not show a significant efficacy advantage over placebo when added to standard riluzole treatment.

How Was the Trial Designed?

The international, randomized, double-blind, placebo-controlled trial enrolled 51 patients who were randomized in a 2:1 ratio to receive either IFB-088 50 mg/day plus riluzole 100 mg/day or placebo plus riluzole 100 mg/day for six months. The primary objective was to assess safety, with secondary endpoints examining efficacy through multiple functional and biomarker measures.

Safety Profile: Comparable but with Notable Differences

Treatment-emergent adverse events (TEAEs) occurred in 73.5% of patients in the IFB-088 group compared to 58.8% in the placebo group. Drug-related TEAEs were reported in 38.2% of IFB-088-treated patients versus 23.5% in the placebo group. Serious adverse events were similar between groups (23.5% in both arms), while fatal TEAEs occurred in 14.7% of IFB-088-treated patients compared to 11.8% in the placebo arm, with two deaths in the IFB-088 group considered possibly related to the study drug.

No Significant Functional Improvements Observed

Regarding efficacy, the trial showed no significant difference between treatment groups in ALS Functional Rating Scale Revised (ALSFRS-R) scores at six months (p=0.923). A post-hoc analysis adjusting for baseline neurofilament light chain (NfL) levels still showed no significant treatment effect (p=0.65). Other functional measures including the ALS Milano-Torino Staging (MITOS) and King's College Scale also showed no significant differences between groups.

Study Limitations and Disease Context

The study, which was conducted at sites in France and Italy, faced some limitations. Investigators noted that biomarker analysis performed by the primary laboratory yielded data below quantification limits and significant coefficient of variation deviations, requiring cautious interpretation of results. Additional biomarker analyses were subsequently performed at another laboratory and used for post-hoc analysis.

Bulbar-onset ALS represents a particularly aggressive form of the disease, characterized by initial symptoms affecting speech and swallowing. This study specifically targeted patients with disease onset within 18 months prior to screening and with relatively preserved functional status (ALSFRS-R score ≥ 36) at baseline.

The Quest for New ALS Treatments Continues

Riluzole, the standard of care treatment used in both arms of the study, remains one of only a few approved treatments for ALS, highlighting the continued need for new therapeutic approaches for this devastating neurodegenerative disease.

Summary

InFlectis BioScience has completed a Phase 2 trial evaluating IFB-088 (icerguastat) in 51 patients with bulbar-onset ALS. The international, double-blind study randomized patients 2:1 to receive either IFB-088 50 mg/day plus riluzole 100 mg/day or placebo plus riluzole for six months. While the drug demonstrated an acceptable safety profile, TEAEs were more frequent in the IFB-088 group (73.5%) than in the placebo group (58.8%). The trial's primary efficacy measures, including ALSFRS-R scores, showed no significant differences between treatment arms (p=0.923), even after post-hoc analysis adjusting for baseline NfL levels. The study, conducted in France and Italy, faced limitations regarding biomarker analysis. These results highlight the continuing challenges in developing effective treatments for bulbar-onset ALS, an aggressive form of the disease characterized by initial speech and swallowing difficulties.