1st Patient Dosed in Basket Trial of ALS Therapy Candidate SLS-005
The first patient has been dosed in an open-label Phase 2 trial that’s evaluating Seelos Therapeutics’ experimental therapy SLS-005 in people with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases associated with the accumulation of toxic protein aggregates.
Called a basket trial because it tests one therapy in several conditions with a common molecular feature, the Australia-based study (ACTRN: 12621001755820) is enrolling up to 18 adults, ages 18–75. These include up to four patients with ALS, up to 10 with Huntington’s disease, and up to four with spinocerebellar ataxia type 3 (SCA3).
“Seelos would like to thank our partners in Australia for their hard work in helping us initiate this basket study,” Raj Mehra, PhD, Seelos’ chairman and CEO, said in a company press release. “We hope to gain valuable insights into the activity of SLS-005 in several devastating neurodegenerative diseases and the open-label design provides a degree of transparency not possible in a blinded study.”
In contrast to blinded trials, open-label studies allow both participants and researchers to know what the participant is receiving. In the current trial, all participants will receive the experimental therapy and there will be no placebo group.
Seelos also announced that the blinded, placebo-controlled Phase 2/3 trial (NCT05136885) of SLS-005 in ALS — running as the fifth arm of the multi-regimen HEALEY ALS platform trial (NCT04297683) — is still recruiting up to 160 ALS patients at more than 30 U.S. sites.
“At its current pace of enrollment, we currently expect it to be fully enrolled by [September],” Mehra said.
Top-line results are anticipated by mid-2023, and should they be positive, the company plans to use them to support filing regulatory applications seeking SLS-005’s approval for ALS.
The therapy’s active ingredient, trehalose, is a natural sugar molecule found in plants, fungi, and bacteria that can reach the brain and promote autophagy. This is the process by which cells break down and recycle old or faulty proteins and components they no longer need, preventing their toxic accumulation.
Administered directly into the bloodstream, SLS-005 has been shown to lower aggregation of faulty proteins and reduce the accumulation of toxic clumps in animal models of neurodegenerative conditions associated with the buildup of toxic material.
In ALS models, it promoted the clearance of ALS-associated TDP-43 and SOD1 proteins, preserving the nerve cells lost in ALS and delaying disease progression. TDP-43 and SOD1 are known to build up to toxic levels in ALS, contributing to nerve cell damage and death.
SLS-005 received orphan drug designation in both the U.S. and the European Union, which is meant to speed its clinical development and regulatory review.
The open-label basket trial will evaluate the safety, tolerability, and effectiveness of SLS-005 in adults whose ALS symptoms started within the past two years and in Huntington’s and SCA3 patients with a confirmed genetic diagnosis.
Participants will receive the therapy at a dose of 0.75 grams per kg of bodyweight once weekly for 24 weeks (nearly six months).
The study’s efficacy goals include assessing changes in physician- and patient-reported outcome measures. These include the Patient Global Impression of Change scale, the Clinical Global Impression of Change scale, the Patient Global Impression of Severity, the Clinical Global Impression of Severity, and the EuroQol visual analogue scale.
For people with ALS, disease progression also will be assessed with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), the Center for Neurologic Study Bulbar Function Scale, and a lung function test.
Those completing the 24-week treatment period may choose to enter an extension phase wherein they’ll continue treatment for an additional 52 weeks (about one year).
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