Mixed Results Announced for Trehalose in ALS Study

Topline data were announced from the phase 2/3 HEALEY ALS Platform trial evaluating SLS-005 (intravenous [IV] trehalose) for amyotrophic lateral sclerosis (ALS).

SLS-005 contains the active ingredient trehalose, a low molecular weight disaccharide (0.342 kDa) that crosses the blood brain barrier, stabilizes proteins, and activates autophagy through the activation of Transcription Factor EB. In preclinical studies, SLS-005 was found to reduce aggregation of misfolded proteins and reduce accumulation of pathologic material. 

The double-blind, placebo-controlled HEALEY ALS Platform trial – Regimen E (ClinicalTrials.gov Identifier: NCT05136885) evaluated the efficacy and safety of SLS-005 in ALS patients. Study participants were randomly assigned 3:1 to receive weekly IV infusions of SLS-005 or placebo. The primary endpoint was the change from baseline on Revised ALS Functional Rating Scale (ALSFRS-R) score at 24 weeks. Secondary endpoints included the change in respiratory function as measured by slow vital capacity (SVC), muscle strength, and comparison of rate occurrence between groups.

Among participants in the Full Analysis Set (FAS), treatment with SLS-005 failed to meet statistical significance in the primary and secondary endpoints with a 13% improvement in function and mortality, and an 88% success probability vs the prespecified 98% success probability. 

While treatment success was not observed in FAS, SLS-005 was favored in a prespecified group of Efficacy Relyvrio Free (ERF) population. FAS included shared placebo from all regimens, including Regimen E (RGE; n=204) and the RGE SLS-005 participants (n=120). ERF (n=99) included participants who followed study protocol as envisioned and excluded participants who initiated Relyvrio during the study. 

Among participants in the ERF data set, treatment with SLS-005 achieved a 22% improvement in the slope of change in ALSFRS-R assessment adjusted for mortality with an 89% success probability at 24 weeks vs placebo. Moreover, the SLS-005 treatment arm had a slower rate of decline in ALSFRS-R slope over 6 months vs placebo (-0.80 vs -1.07 per month, respectively). The slowing of SVC decline was -11.5% in the SLS-005 arm at 24 weeks vs -15.4% in the placebo arm.

The Company intends to run additional analyses once the full study dataset is available, including biomarkers of neurodegeneration, neurofilament light chain, exploratory efficacy results, subgroups and post-hoc analyses. 

“The HEALEY platform is designed to detect signals of efficacy and we believe the observed signal and success probability is competitive to other recently FDA-approved therapies for ALS which also failed to achieve statistical significance when measured for function and mortality on similar primary and efficacy endpoints,” said Raj Mehra PhD, Chairman and CEO of Seelos. “We plan to request a meeting with the FDA to discuss potential next steps for the program and will continue our potential partner discussions.”

The Food and Drug Administration previously granted Orphan Drug designation to SLS-005 for this indication.

This article originally appeared on MPR