Seelos Therapeutics has received a notification from the U.S. Food and Drug Administration (FDA) permitting the launch of its Phase 2b/3 clinical trial investigating SLS-005 (trehalose) as a treatment for amyotrophic lateral sclerosis (ALS).
Seelos plans to enroll 160 patients with either familial or sporadic (of unknown cause) ALS for the trial, with the primary goal of determining the effectiveness of SLS-005 at delaying the progression of the disease.
“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,” Raj Mehra, PhD, chairman and CEO of Seelos, said in a press release. “Receiving the FDA notice that we may begin a registrational Phase IIb/III study is a transformative event for Seelos and our hope is that SLS-005 can offer a potential option for patients.”
ALS is a neurodegenerative disorder that results in the dysfunction and death of motor neurons, the nerve cells responsible for muscular movement.
Mutations in a number of genes, including C9orf72, SOD1, FUS, and TARDBP, are all known to contribute to the development of ALS. These genetic mutations can cause the build-up of proteins like TDP-43, SOD1, and SQSM1/p62, which aggregate in motor neurons and eventually cause them to die.
The active ingredient in SLS-005 is a sugar molecule called trehalose that is naturally produced in some bacteria, fungi, plants, and invertebrate animals, but is not found in mammalian cells.
Studies have found that trehalose is able to cross the blood-brain barrier in humans, and influence cellular behavior by stabilizing proteins and activating autophagy, cells’ “digestive system” that removes and recycles damaged cellular components, clearing toxic protein clumps.
The blood-brain barrier is a semipermeable membrane that protects the brain from the external environment and is a major barrier for the efficient delivery of certain therapeutics that need to reach the central nervous system (brain and spinal cord).
Pre-clinical studies have shown that SLS-005 is able to increase the removal of TDP-43 and decrease the formation of SOD1 and SQSM1/p62 aggregates. These changes at the molecular level are able to delay the progression of ALS symptoms, preserve motor neurons and increase the size of muscle fibers.
“Several preclinical studies have demonstrated the potential of trehalose as a treatment for ALS, demonstrating preservation of motor neurons, motor function and prolonged survival,” said Warren Wasiewski, MD, chief medical officer of Seelos. “We are excited to start our clinical program for this devastating disease.”
In the planned Phase 2b/3 trial, patients will receive either SLS-005 or a placebo. Disease progression will be measured using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), which measures 10 attributes of the disease on a 0–4 scale, with a total score of 40 conferring maximum functionality.
After 24 weeks of receiving either the treatment or the placebo, researchers will compare baseline ALSFRS-R scores to the current scores as a determinant of SLS-005 effectiveness.
Secondary efficacy goals include measures of slow vital capacity (volume of air expired under non-forced conditions), muscle strength, quality of life, and other signs of disease progression.
With FDA approval to launch this trial, Seelos intends to make ALS the lead indication for the treatment.
However, SLS-005 also is being investigated by Seelos as a treatment for other indications, including Sanfilippo syndrome, oculopharyngeal muscular dystrophy (OPMD), and spinocerebellar ataxia type 3 (SCA3).
“The FDA signoff to begin this pivotal study allows Seelos to focus on ALS as the lead indication for SLS-005,” said Mehra. “We remain committed to our work in additional indications as well.”
In two Phase 2 trials investigating SLS-005 as a treatment for OPMD (NCT02015481) and SCA3 (NCT02147886), data collected from 70 enrolled patients indicated that SLS-005 was safe and well-tolerated in patients.
SLS-005 recently waas granted orphan drug status by the FDA for the treatment of Sanfilippo syndrome, and also was granted approval from the FDA to launch a Phase 2b/3 clinical trial with Sanfilippo patients.
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