Seelos Therapeutics Provides Update On Top-Line Results From Its Amyotrophic Lateral Sclerosis Study With SLS-005

Author: Benzinga Newsdesk | March 19, 2024 08:20am

Seelos Therapeutics, Inc. (NASDAQ:SEEL) ("Seelos"), a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases, today provided an update on top-line data of the Phase 2/3 HEALEY ALS Platform trial. This study was performed in collaboration with The Sean M. Healey and AMG Center, which is viewed as an influential force in ALS research and in caring for the ALS community. Their unique and innovative approach continues to be a benefit to the ALS community and its contributions have helped bring the last two FDA approved therapies for ALS to market.

 

We plan to request a meeting with the FDA to discuss potential next steps for the program

The study was designed to evaluate SLS-005 (IV trehalose), a low molecular weight disaccharide that stabilizes misfolded proteins and activates autophagy, in decreasing the slope of the ALS Functional Rating Scale (ALSFRS-R) and separation from placebo in Function and Mortality in an all-comers population of Persons with ALS (PALS).

While the study did not meet statistical significance in the primary and secondary endpoint in the Full Analysis Set (FAS)2, by showing a 13% improvement in Function and Mortality with an 88% success probability (versus the pre-specified 98%), it showed a potential signal of efficacy in a pre-specified subgroup (ERF)1.

In the pre-specified subgroup of PALS treated with SLS-005, without RELYVRIO®, the top-line data favored SLS-005 versus placebo in efficacy measures in the Efficacy RELYVRIO® Free (ERF)1 data set (n=130), including:

• a 22% improvement in slope of change in ALSFRS-R assessment adjusted for mortality, with an 89% success probability, at 24 weeks
• the rate of decline in ALSFRS-R slope (points per month) also favored the SLS-005 treatment group versus placebo over 6 months (-0.80 and -1.07 points per month, respectively)
• a 25% slowing of Slow Vital Capacity (SVC) decline versus placebo (-11.5% for SLS-005 and -15.4% for placebo) at 24 weeks

Additional analysis and information from these data accessible here.  

"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 Ph.D., Chairman and Chief Executive Officer 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."

Seelos has not yet received the full dataset and upon receiving it in the near future, Seelos plans to run additional analyses, including biomarkers of neurodegeneration, neurofilament light chain (NfL), exploratory efficacy results, subgroups and post-hoc analyses. SLS-005 was generally well-tolerated and comparable to placebo in safety. There was an imbalance of deaths/death equivalents observed in the study, with more events seen in the SLS-005 group compared to placebo, all were considered unrelated to the study drug.

Populations – ERF1, FAS2 and ERO3:

Seelos received top-line results for Regimen E (RGE).  This included a Full Analysis Set (FAS), an Efficacy Regimen Only (ERO) population and an Efficacy RELYVRIO® Free (ERF) population. FAS includes shared placebo from all regimens, including RGE (n=204) and the RGE SLS-005 participants (n=120). The Efficacy Regimen Only (ERO) population includes 120 RGE SLS-005 and 41 RGE placebo participants. 31 participants in the ERO population received RELYVRIO® during the SLS-005 RGE study, thus confounding results from this population. The ERF analyses exclude participants who initiated RELYVRIO® during the study. ERF represents the participants who followed the protocol as envisioned (n=130, i.e., the ERF population comprises 81% of ERO/RGE participants).

About SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion)

SLS-005 is a low molecular weight disaccharide (0.342 kDa) that crosses the blood brain barrier and is thought to stabilize proteins and activate autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. The activation of TFEB is an emerging therapeutic target for a number of diseases with pathologic accumulation of storage material. In animal models of several diseases associated with abnormal cellular protein aggregation or storage of pathologic material, SLS-005 has been shown to reduce aggregation of misfolded proteins and reduce accumulation of pathologic material. SLS-005 has previously received Orphan Drug Designation for the treatment of ALS from the U.S. Food and Drug Administration and from the European Medicines Agency in the EU.  SLS-005 is an investigational treatment and is not currently approved by any health authority for medicinal use.

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