The Food and Drug Administration (FDA) has issued a may proceed notice, allowing the initiation of a phase 2b/3 trial studying trehalose (SLS-005, Seelos Therapeutics, New York, NY) for the treatment of amyotrophic lateral sclerosis (ALS).
Familial ALS is caused by mutations in the C9orf72, SOD1, FUS, and TARDBP genes and these are also thought to contribute to the development of sporadic ALS. These mutations contribute to the death of motor neurons and ALS affected motor neurons develop a buildup of protein aggregates such as TDP-43 and SOD1. In in-vivo studies of ALS, trehalose has been shown to increase clearance of TDP-43, decrease SOD1 and SQSM1/p62 aggregates and monomers, delay the progression of the disease, preserve ventral horn motor neurons,and increase muscle fiber size.
"ALS is a debilitating disease which currently lacks a cure and there is significant evidence suggestive of trehalose having the potential to alter or slow the progression of ALS," said Raj Mehra PhD, chairman and chief executive officer of Seelos. "Receiving the FDA notice that we may begin a registrational phase 2b/3 study is a transformative event for Seelos and our hope is that SLS-005 can offer a potential option for patients. The FDA signoff to begin this pivotal study allows Seelos to focus on ALS as the lead indication for SLS-005. We remain committed to our work in additional indications as well."
The phase 2b/3 trial plans to enroll 160 participants with either familial or sporadic ALS in a double-blind placebo-controlled trial. Participants will be randomly assigned 3:1 to receive drug or placebo. Change from baseline on revised ALS functional rating scale (ALSFRS-R) score at 24 weeks will be the outcome measure. Secondary endpoints will also be measured at 24 weeks, including change from baseline in slow vital capacity, muscle strength, quality of life measurements as well as additional signs of disease progression.
"Several preclinical studies have demonstrated the potential of trehalose as a treatment for ALS, demonstrating preservation of motor neurons, motor function, and prolonged survival. We are excited to start our clinical program for this devastating disease," said Warren W. Wasiewski, MD, FAAP, chief medical officer of Seelos.
Fabio Fieni Toso, MD; Rene de Araújo Gleizer, MD; and Lívia Almeida Dutra, MD, PhD
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH