RARE Daily

Seelos Says ALS Trial Fails, but Shows Potential Signs of Efficacy in Subgroup

March 20, 2024

Rare Daily Staff

Seelos Therapeutics in an update on top-line data from its phase 2/3 of its experimental therapy for the rare and deadly neurodegenerative disease ALS, said it failed to meet statistical significance in the primary and secondary endpoints but showed a potential signal of efficacy in a pre-specified subgroup.

Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch, and waste away. Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive with most people with ALS eventually dying from respiratory failure, usually within three to five years from when the symptoms first appear. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease.

The study, which was performed in collaboration with The Sean M. Healey and AMG Center,  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 people with ALS.

A 1-point change in the ALSFRS-R score can indicate a meaningful difference in a person’s ability to function independently with activities of daily living (ADL’s), including eating, bathing, dressing, or walking.

In the pre-specified subgroup of patients with ALS 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, including a 22 percent improvement in slope of change in ALSFRS-R assessment adjusted for mortality, with an 89 percent 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). Additionally, there was a 25 percent slowing of Slow Vital Capacity decline versus placebo at 24 weeks.

“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, 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.”

Seelos said it has not yet received the full dataset and plans to run additional analyses when it receives it, 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 of which were considered unrelated to the study drug.

Photo: Raj Mehra, chairman and CEO of Seelos

 

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