A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

<a href="https://seelostherapeutics.com/sls-005-trehalose/">SLS-005</a> did not significantly slow <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) progression compared with a placebo in the HEALEY platform trial, according to top-line data showing that the experimental therapy did not ease functional declines nor extend patient survival.
The therapy, developed by <a href="https://seelostherapeutics.com/">Seelos Therapeutics</a>, also failed to slow declines in muscle strength and lung function, which, overall, means the trial failed to meet its primary and key secondary measures.
“Though we did not achieve success with this trial, we remain committed to using the data to advance ALS science, and our experience with the trial to understand ALS,&#8221; Merit Cudkowicz, MD, principal investigator and sponsor of the HEALEY ALS Platform Trial, said in a <a href="https://www.massgeneral.org/neurology/als/news/healeyamg-announces-platform-trial-update">press release</a>.
“We are thankful to the many people who participated in this study. We will learn from these results and continue to use this data to inform future advances in ALS trial design,” added Cudkowicz, who is also director of the Sean M. Healey &amp; AMG Center for ALS, chief of the Department of Neurology at Massachusetts General Hospital (MGH), and the Julieanne Dorn Professor of Neurology at Harvard Medical School.
[recommended-reading id=83732]
<h3>SLS-005 aims to slow ALS progression by breaking down toxic protein clumps</h3>
SLS-005 contains trehalose, a natural sugar molecule that promotes autophagy, which is a cellular recycling process that helps break down old and faulty proteins. In so doing, it prevents them from toxically accumulating in cells.
The therapy was designed to slow ALS progression by entering the brain and breaking down these toxic protein clumps. Such clumps, or aggregates, contribute to nerve cell death in the neurodegenerative disease.
SLS-005 was assessed in the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a> — a novel approach to drug testing in which multiple ALS therapy candidates are investigated simultaneously against a shared placebo group. Dubbed a perpetual trial, HEALEY continues to <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1#contacts">enroll adults</a> with ALS whose first symptoms occurred within the last three years.
The trial is ongoing at dozens of U.S. sites. Once a participant is deemed eligible through the trial’s master protocol, he or she can be randomly assigned to any active treatment arm.
The <a href="https://clinicaltrials.gov/ct2/show/NCT05136885">SLS-005 arm (NCT05136885)</a> enrolled 161 patients: Among them, 120 received weekly SLS-005 infusions into the bloodstream, and the rest, a placebo.
The participants also could continue to use a stable regimen of <a href="https://alsnewstoday.com/approved-treatments-for-als/">approved ALS therapies</a>, consisting of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone) or riluzole (e.g., Rilutek, Tiglutik, Exservan). <a href="https://alsnewstoday.com/amx0035/">Relyvrio</a> (sodium phenylbutyrate and taurursodiol) was approved about eight months after the SLS-005 trial arm began enrollment, and some participants also ended up receiving that newly approved medication along with their assigned treatment.
As with all arms of the platform trial, the main goal was to evaluate whether SLS-005 could significantly slow disease progression relative to the placebo over 24 weeks, or about six months.
Progression was assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), which measures a person&#8217;s ability to perform activities of daily living, such as turning in bed, gripping a pen, climbing stairs, speaking, and breathing.
[recommended-reading id=41326]
<h3>Monthly declines in ALSFRS-R scores seen in SLS-005, placebo groups</h3>
Seelos now has reported that the trial’s goal was not met, with patients in the SLS-005 arm and the shared placebo group seeing similar monthly declines in ALSFRS-R scores.
In an analysis accounting for functional declines and mortality, SLS-005 was associated with a 13% delay in disease progression or death; however, these differences failed to reach statistical significance. Similarly to the primary goal, other key secondary endpoints, such as muscle strength and respiratory function, also were not met.
[quote=&#8221;center&#8221;]Even though the trial results were negative, participants&#8217; involvement in the trial contributed greatly to ALS research by providing substantial clinical and biomarker data that will help us better understand ALS disease mechanisms and the role of the cellular catalysts in people living with ALS and may help unlock keys to the next ALS treatment.[/quote]
“We would like to extend our sincere gratitude to participants in the trehalose regimen who committed their invaluable time and energy in the trial as well as the NEALS investigators and study staff for their dedicated effort and expertise,&#8221; said Shafeeq Ladha, MD, Barrow Neurological Institute and co-lead investigator of the trehalose regimen.
“Even though the trial results were negative, participants&#8217; involvement in the trial contributed greatly to ALS research by providing substantial clinical and biomarker data that will help us better understand ALS disease mechanisms and the role of the cellular catalysts in people living with ALS and may help unlock keys to the next ALS treatment,” Ladha added.
Seelos, however, shared some data suggesting that SLS-005 may have benefited a subset of patients who did not simultaneously receive Relyvrio while in the trial. Relyvrio was <a class="c-link" href="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/" data-sk="tooltip_parent">approved in the U.S.</a> in 2022, but now is being withdrawn after it failed to show efficacy in a clinical trial.
During the SLS-005 trial, while it wasn&#8217;t initially planned for, some participants ultimately started using Relvvrio. Seelos believes this mid-trial addition could confound the results, and noted that, by removing those individuals, the analysis is cleaner and more in line with how the data appeared originally.
For its part, SLS-005 was generally well tolerated. More deaths occurred in the SLS-005 group, but none were considered related to treatment. Seelos notes that it plans to run additional analyses, including those related to biomarkers and patient subgroups, as the data become available.
The company now is also planning to meet with the U.S. Food and Drug Administration (FDA) to discuss the next steps for SLS-005&#8217;s development.
“We believe the observed signal and success probability is competitive to other recently FDA-approved therapies for ALS,&#8221; Raj Mehra, PhD, chairman and CEO of Seelos said in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-provides-update-on-top-line-results-from-its-amyotrophic-lateral-sclerosis-als-study-with-sls-005-iv-trehalose-302092918.html">company press release</a>. &#8220;We plan to request a meeting with the FDA to discuss potential next steps for the program.”

Infusion therapy SLS-005 fails to slow ALS progression in trial

An expanded access program for the experimental treatment <a href="https://seelostherapeutics.com/sls-005-trehalose/" rel="nofollow">SLS-005</a> has dosed its first participant, according to <a href="https://seelostherapeutics.com/" rel="nofollow">Seelos Therapeutics</a>, the therapy&#8217;s developer.
The <a href="https://alsnewstoday.com/news/funding-expands-access-seelos-investigational-als-therapy-sls-005/">expanded access program</a>, or EAP, is an open-label study allowing access to SLS-005 for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who are not eligible for ongoing clinical trials, including an ongoing Phase 2/3 study of this potential therapy.
Conducted in collaboration with the Sean M. Healey &amp; AMG Center for ALS at Massachusetts General Hospital, the program expects to enroll about 70 adults who will be treated for six months. Contact information for the SLS-005 clinical program is available on a <a href="https://seelostherapeutics.com/healey-als-platform-trial-regimen-e-sls-005-trehalose/" rel="nofollow">Seelos webpage</a>.
[recommended-reading id=78353]
<h3>Trehalose in SLS-005 may help nerve cells to clear toxic proteins</h3>
&#8220;Initiating this EAP is an important event for Seelos and for patients in need of therapy who cannot participate in existing clinical trials,&#8221; Raj Mehra, PhD, chairman and CEO of Seelos, said in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-doses-the-first-amyotrophic-lateral-sclerosis-als-patient-with-sls-005-in-an-expanded-access-program-301788950.html">company press release</a>.
SLS-005 contains a naturally occurring sugar molecule called trehalose that is given as an infusion into the bloodstream. The therapy can enter the brain and is thought to promote autophagy, a recycling process used by cells to break down complex molecules they no longer need.
By activating this process, SLS-005 may help to clear the toxic clumps of proteins in nerve cells that are believed to help drive ALS. The therapy has been designated an orphan drug, a status that aims to incentivize the development of treatments for rare disorders, in <a href="https://alsnewstoday.com/news-posts/2020/11/20/fda-grants-orphan-drug-designation-to-seelos-sls-005-for-treating-als/">the U.S.</a> and the <a href="https://alsnewstoday.com/news-posts/2021/06/04/ema-orphan-drug-designation-sls-005-als/">European Union</a>.
SLS-005 is currently part of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>, a clinical trial run by scientists at Massachusetts General to simultaneously test several potential ALS treatments against a shared placebo.
The trial&#8217;s <a href="https://clinicaltrials.gov/ct2/show/NCT05136885">SLS-005 arm (NCT05136885)</a> has <a href="https://alsnewstoday.com/news/enrollment-complete-als-phase-2-3-trial-sls-005/">finished enrolling 160 people</a> with ALS. Three-quarters of the participants are being treated with weekly injections of SLS-005, while the rest are getting weekly placebo injections. Its main goal is to assess whether treatment slows disease progression, as measured by changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, and results are expected later this year.
The EAP is being conducted in parallel to the HEALEY trial, and it is funded by a grant from the National Institute of Neurological Disorders and Stroke (NINDS), given under the <a href="https://alsnewstoday.com/news/landmark-act-for-als-act-president-biden/">Accelerating Access to Critical Therapies for ALS Act</a> (ACT for ALS).
&#8220;We are grateful for the support from the ALS community, the Healey platform team and for the funding from NINDS,&#8221; Mehra said.
Seelos is also developing SLS-005 as a potential treatment for spinocerebellar ataxia (SCA), a genetic neurological disorder. The company recently announced, in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-announces-business-update-on-its-key-programs-301785089.html">separate press release</a>, that it is pausing enrollment of a clinical trial testing SLS-005 in SCA.
This decision was made purely due to business considerations, according to Seelos, and will allow more resources to be focused toward developing the therapy for ALS.

Expanded access program for SLS-005 begins treating first ALS patient

<a href="https://seelostherapeutics.com/">Seelos Therapeutics</a> has finished enrolling patients in its Phase 2/3 clinical trial of <a href="https://seelostherapeutics.com/sls-005-trehalose/">SLS-005</a> to treat <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), the company announced.
The <a href="https://clinicaltrials.gov/ct2/show/NCT05136885">ongoing trial (NCT05136885)</a> recruited 160 patients with <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial</a> and <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic ALS</a>, and top-line results are expected by the second half of 2023.
This is the fifth arm of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>, which is being led by researchers at the Sean M. Healey &amp; AMG Center for ALS at Massachusetts General Hospital (MGH), Boston to investigate several ALS therapies simultaneously against a shared placebo group.
The company also expects to launch an <a href="https://alsnewstoday.com/news/funding-expands-access-seelos-investigational-als-therapy-sls-005/">expanded access program</a> (EAP) in the coming months to give people with ALS who aren&#8217;t eligible for clinical trials the opportunity to access SLS-005. The EAP will include 70 participants who&#8217;ll receive the experimental therapy for 24 weeks. <a href="https://seelostherapeutics.com/patients-and-caregivers/">More information</a> is available at Seelos&#8217; website.
&#8220;The full enrollment of this study is a significant milestone for Seelos. We look forward to releasing the top-line data later this year and initiating the Expanded Access Program later this quarter,&#8221; said Raj Mehra, PhD, Seelos’ chairman and CEO, in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-announces-completion-of-enrollment-of-its-phase-iiiii-trial-of-sls-005-in-amyotrophic-lateral-sclerosis-on-the-healey-als-platform-301744494.html">company press release</a>.
EAP will be funded by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the <a href="https://alsnewstoday.com/news/landmark-act-for-als-act-president-biden/">Accelerating Access to Critical Therapies for ALS Act</a> (ACT for ALS).
&#8220;We would like to offer our gratitude to the ALS community for its support and to the team at Healey &amp; AMG Center for ALS at Mass General and the clinical trial sites in the Northeast ALS Consortium for their hard work and commitment in running this innovative platform trial. We also thank the NINDS for the financial support of the Expanded Access Program grant under the ACT for ALS,&#8221; Mehra said.
[recommended-reading id=81946]
<h3>SLS-005 promotes protein clearance</h3>
SLS-005 is made of a natural sugar molecule called trehalose that can enter the brain and promote autophagy, the process by which cells break down and recycle old or faulty proteins they no longer need, preventing their toxic buildup.
Administered directly into the bloodstream, SLS-005 has been shown to lower faulty proteins&#8217; aggregation and reduce the accumulation of toxic clumps in animal models of neurodegenerative conditions.
In ALS models, it promoted the clearance of TDP-43 and SOD1 proteins, which are known to accumulate to toxic levels and contribute to nerve cell death. By doing so, the treatment was able to prevent nerve cell loss and delay disease progression in these models.
SLS-005 received orphan drug status — a designation that&#8217;s intended to speed the development and review of therapies for life-threatening rare diseases — in both <a href="https://alsnewstoday.com/news-posts/2020/11/20/fda-grants-orphan-drug-designation-to-seelos-sls-005-for-treating-als/">the U.S.</a> and the <a href="https://alsnewstoday.com/news-posts/2021/06/04/ema-orphan-drug-designation-sls-005-als/">European Union</a>.
In the SLS-005 arm of the HEALEY ALS platform trial, participants were randomly assigned to weekly intravenous (into-the-vein) injections of SLS-005 or a placebo for 24 weeks (about six months). The patients were randomized in a 3:1 ratio, meaning for each patient assigned a placebo, three were given SLS-005.
The trial’s main goal is to evaluate whether SLS-005 slows disease progression, as measured with the ALS Functional Rating Scale Revised (ALSFRS-R). Secondary goals include changes in lung function, muscle strength, and quality of life, as well as symptoms of disease progression.
Other treatments being investigated in the HEALEY trial include Prilenia Therapeutic’s pridopidine <a href="https://clinicaltrials.gov/ct2/show/NCT04615923">(NCT04615923)</a> and Clene Nanomedicine‘s CNM-Au8 <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">(NCT04414345)</a>.
Another regimen, UCB’s zilucoplan <a href="https://clinicaltrials.gov/ct2/show/NCT04436497">(NCT04436497)</a>, was <a href="https://alsnewstoday.com/news/ucb-stops-zilucoplan-arm-early-healey-trial-als-lack-of-efficacy/">discontinued in March 2022</a> due to a lack of effectiveness in an interim analysis. Biohaven Pharmaceuticals’ verdiperstat <a href="https://clinicaltrials.gov/ct2/show/NCT04436510">(NCT04436510)</a> also <a href="https://alsnewstoday.com/news/als-therapy-verdiperstat-fails-healey-trial-efficacy-goals/">failed to meet</a> its primary and secondary goals.

Tag: SLS-005

Infusion therapy SLS-005 fails to slow ALS progression in trial

Expanded access program for SLS-005 begins treating first ALS patient

Enrollment complete in HEALEY Phase 2/3 trial arm of SLS-005