Our bimonthly Clinical Research & Trials Update keeps you up to date on what’s happening in ALS clinical research. We unpack trial press releases, flag upcoming studies, and highlight important new publications, including care guidelines, long-term therapy data, and off-label treatment insights.
For other news on lab-based ALS research using animal models and emerging therapeutic approaches, read our Fundamental Research Updates.
Read more and see all Canadian trials on our clinical trials database.
We encourage people affected by ALS to approach media coverage and press releases about ALS research and clinical trials with caution. These announcements are often designed for investors and usually highlight early or incomplete findings. If you have questions about a specific therapy or study, speak with your clinician or attend our Ask Us Anything: Research sessions to help make sense of the information and what it may mean for you.
Novartis has discontinued its Phase 2 ASTRALS trial evaluating VHB937 after the study did not meet its primary goals. VHB937 is an antibody designed to target TREM2, a protein found on microglia, the immune cells of the brain and spinal cord. Researchers hoped the treatment could help shift these cells away from potentially harmful inflammatory activity and boost their normal, protective functions.
For clinical trials that fail to demonstrate a benefit for ALS, the most important thing we can hope for is to learn from them and evolve our understanding of the disease based on the results. At this time, Novartis has not released detailed trial results. As more information becomes available published by the company, we will provide updates.
* Neurofilament light (NfL) is a protein released when neurons are damaged and can be detected in the cerebrospinal fluid and blood. In ALS, higher NfL levels are generally associated with more rapid disease progression, at a group level. In clinical trials, NfL is evolving as a biomarker to help researchers understand whether a treatment may be reducing underlying motor neuron damage. NfL levels tend to rise during presymptomatic and early disease and then stabilize or plateau as the disease progresses, and when a substantial and sustained drop occurs with treatment, benchmarked at 30%, it is considered meaningful. Reductions of less than 30% are difficult to reliably attribute to an effect of the treatment.
Clene has announced additional analyses of the data from CNM-Au8, previously investigated in a Phase 2 trial as part of the HEALEY ALS Platform Trial, and in a smaller Phase 2 trial called RESCUE-ALS.
Original data from the trials showed no benefit demonstrated by the study endpoints, including measures of function and disease progression. However, after the trial ended, Clene conducted additional exploratory analyses (called post-hoc analysis), looking more closely at specific groups of participants and other outcomes that were not part of the original main study. Clene reported that these analyses seemed to suggest some benefit for subgroups. Based on this, the company had announced that they intend to run a confirmatory Phase 3 trial (RESTORE-ALS).
Clene has now released additional analyses exploring neurofilament light chain (NfL)* in the past trials.
Results reported:
What needs to be considered:
Clene plans to include these analyses in its regulatory submission as it seeks accelerated approval for CNM-Au8 in the U.S. If the treatment advances to a Phase 3 trial, researchers will need to decide ahead of time which patient groups, biomarkers (such as NfL), and other outcomes they want to study. Including these questions in the original trial plan will help ensure the results provide more reliable answers.
NeuroSense has reported new Phase 2 PARADIGM results for PrimeC, including data related to TDP-43, a key hallmark protein of ALS. Read our full news story to learn what was found and what it could mean.
EXPERTS-ALS, a platform trial testing multiple potential ALS treatments, has discontinued two drug arms after an interim analysis found they were unlikely to provide meaningful benefit. Read our full news story to learn what this means.
ProJenX has announced new data from its Phase 1b study of prosetin, which had sites in Canada. The study, which included 41 participants with ALS, found that prosetin was generally safe and well tolerated, with no treatment-related serious adverse events reported. Researchers also found evidence that the drug was engaging its intended biological target.
Participants are continuing in a long-term extension study, and the data collected will help guide the design of a future Phase 2 trial. Larger and later-stage studies will hopefully determine whether prosetin can slow ALS progression or improve function.
Watch our ALS Clinical Trials Unboxed on Prosetin, featuring the study investigators who explain the drug and the research behind it.
Amylyx has announced new data from the ongoing Phase 1 LUMINA trial of AMX0114. In the first group of participants treated with a lower dose of the drug, the treatment appeared to be generally safe and well tolerated, with no serious side effects linked to the drug.
Based on these findings, the trial has advanced to test higher doses of AMX0114. The second dosing group is fully enrolled, and recruitment is underway for a third, higher dose group at sites in the U.S. and Canada.
As an early-stage Phase 1 trial, the study is designed primarily to evaluate safety, tolerability, and how the drug behaves in the body. Larger and later-stage studies will be needed to determine whether AMX0114 can slow ALS progression or improve function.
Learn more about AMX0114 and other active ALS clinical trials on our clinical trials page.
In this study, researchers surveyed professionals from 42 companies involved in ALS drug development to better understand the challenges they face. Respondents identified three major scientific barriers: the wide variation in how ALS progresses between people, the lack of reliable biomarkers that can predict or track treatment effects, and the limitations of current clinical outcome measures. Operational challenges, such as funding constraints, participant dropout, and staffing shortages, were also frequently reported. The findings highlight growing support for greater standardization in ALS trial design and the development of better biomarkers, which could help reduce uncertainty and improve the chances of identifying effective treatments.
ALS varies considerably from person to person, making it difficult for clinical trials to detect whether a treatment is working. This review by researchers supported by ALS Canada explores strategies to address that challenge by grouping participants based on characteristics such as genetics, disease progression rate, biomarkers like neurofilament light chain (NfL), imaging findings, or machine learning-based classifications. The authors suggest that enrolling more biologically similar participant groups could make it easier to detect treatment effects and support the development of more personalized therapies. However, they caution that overly restrictive enrollment criteria could limit who can participate and make findings less broadly applicable to the wider ALS population.
The ALS Functional Rating Scale-Revised (ALSFRS-R) is one of the most commonly used measures in ALS clinical trials, but this study found that researchers analyze it in many different ways. Reviewing 45 completed trials, the authors identified 39 different statistical approaches and found that the choice of analysis method could substantially influence study results. Some approaches increased the risk of false-positive findings, while others reduced the ability to detect a real treatment effect. The study highlights the need for greater consistency in how ALSFRS-R data are analyzed, which could improve the reliability, comparability, and interpretation of trial results across the field.
These considerations also highlight the importance of interpreting positive trial findings with appropriate caution, particularly when they emerge from exploratory analyses. Different analytical approaches can sometimes produce different results, which is why findings are considered more reliable when they are confirmed in pre-specified trial aims, independently reproduced, and ultimately evaluated through larger Phase 3 trials and regulatory review processes.
In this funded project, using MRI data from nearly 200 people living with ALS, researchers applied machine learning to identify distinct patterns of disease-related brain changes. The data comes from the Canadian ALS Neuroimaging Consortium (CALSNIC), a national research initiative also supported by ALS Canada that brings together imaging and clinical data from ALS clinics across the country.
The study’s findings seem to identify three distinct ALS subtypes, each associated with different patterns of brain involvement, rates of progression, and survival outcomes, as well as a fourth group that appeared to represent an earlier stage of disease with more favorable outcomes. The findings reinforce a growing idea by some researchers that ALS is not a single disease but a collection of biologically distinct subtypes. Better understanding these differences could help researchers design more targeted clinical trials, improve prediction of disease progression, and ultimately support the development of personalized treatment approaches. An important next step would be for international collaborations to explore if the findings can be independently replicated, with the hope that the results could get closer to being incorporated into clinical trial practice as soon as possible.
Bulbar symptoms, which affect speech and swallowing, often require people living with ALS to make difficult decisions about interventions and supportive care. Through interviews with patients attending a multidisciplinary ALS clinic, researchers supported by ALS Canada found that uncertainty about disease progression often made decision-making challenging. Participants emphasized the importance of receiving clear, personalized information and wanted healthcare providers to tailor discussions to their individual values, preferences, and decision-making styles. The study highlights the importance of person- and family-centred care and suggests that improved decision-making support may help people living with ALS feel more confident when navigating treatment options related to speech and swallowing.
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