The phase 2b/3 study will enroll 160 patients with either familial or sporadic ALS with a primary end point in change from baseline on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score at 24 weeks.
Merit Cudkowicz, MD
Seelos Therapeutics announced that the Seelos’ phase 2b/3 study of SLS-005 (trehalose) has been selected by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital to be included in the HEALEY ALS Platform Trial, the first ever platform trial for the treatment of amyotrophic lateral sclerosis (ALS).1
The investigational new drug (IND) application for the platform trial was approved by the FDA in January 2020, ultimately granting a “may proceed” to 3 of the 5 drugs selected by the Therapy Evaluation Committee: CNM-Au8 (Clene Nanomedicine), verdiperstat (Biohaven Pharmaceuticals), and zulicoplan (Ra Pharmaceuticals).2
The selected investigational agents are all first-in-class biotherapeutic innovations that were developed to treat neurodegenerative disorders, although not necessarily targeting ALS. Now, SLS-005 joins that list.
"We are excited to work with Seelos and look forward to studying SLS-005 in an accelerated format through the HEALEY ALS Platform Trial,” Merit Cudkowicz, MD, director, Sean M. Healey & AMG Center for ALS, and chief of the department of neurology, Massachusetts General Hospital, and principal investigator of the trial, said in a statement.1 “The design team will work closely with Seelos on their regimen specific protocol as well as completing required steps with the central ethics review board and the FDA.”
SLS-005 is a low molecular weight disaccharide that crosses the blood-brain barrier, stabilizes proteins, and activates autophagy. That activation occurs through the activation of the Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression.
Last month, the FDA granted orphan drug designation for SLS-005 for the treatment of ALS.
Seelos’ phase 2b/3 trial, which used as the registered study in the platform trial, will enroll 160 patients with either familial or sporadic ALS. Patients will be randomized 3:1 to either SLS-005 or placebo and evaluated on change from baseline on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score after 24 weeks.3
Secondary end points of the study will also be measured at 24 weeks, including change from baseline in slow vital capacity, muscle strength, quality of life measures as well as additional signs of disease progression.
"The inclusion of the registrational phase 2b/3 study of SLS-005 in this first ever platform trial is the result of extensive work identifying trehalose as a potential treatment to study in ALS,” Raj Mehra, PhD, chairman and chief executive officer, Seelos, said in a statement. “The Healey Center’s recognition of this potential therapy is a major validation and being part of this platform trial should help to expedite the trial by helping to provide greater access to patients.”
The agent was also previously granted orphan drug designation for Sanfilippo syndrome, spinocerebellar ataxia type 3 (SCA3) and oculopharyngeal muscular dystrophy (OPMD).
The Healey Center received approximately 30 applications from 10 countries from its initial request for proposals. Ultimately, the center’s Therapy Evaluation Committee selected those 5 therapies, with IC14 and pridopine as the only 2 who have yet to be cleared by the FDA.
CNM-Au8, which was among the originally listed drugs, is described as an orally administered, concentrated, aqueous suspension of pure faceted nanocrystalline gold that acts catalytically to support various intracellular biological reactions. The orally administered verdiperstat is an irreversible inhibitor of the enzyme myeloperoxidase (MPO), which is associated with increased oxidative stress and inflammation levels in the brain and spinal cord, according to Irfan Qureshi, MD, vice president, neurology, Biohaven Pharmaceutical from an interview with NeurologyLive in February
Qureshi added, “the presence of large numbers of activated microglia is 1 of the hallmarks of neurodegeneration in ALS. MPO is a powerful pro-oxidant enzyme that is present in activated immune cells, including microglia. Inhibiting MPO is anticipated to ameliorate these pathological mechanisms, which are strongly implicated in the onset and progression of ALS.”
Zilucoplan is a macrocytic peptide that binds to complement C5 to inhibit its cleavage into C5a and C5b in activation pathways, which have been linked with inflammation that can contribute to chronic central nervous system diseases.
Sabrina Paganoni, MD, PhD, assistant professor of PM&R, Harvard Medical School and coprincipal investigator of the platform trial, told NeurologyLive in February that the research team will work to incorporate IC14, pridopine, and several other therapies that were not included in the IND.