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 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, consider speaking with your clinician or attending our Research and Clinical Trials 101 Q&A Drop-In to help make sense of the information and what it may mean for you.
* The ALSFRS-R is a widely used clinical tool to measure disease progression in people living with ALS. It evaluates an individual’s ability to perform everyday tasks and tracks decline over time. Through a structured interview, the clinician or patient assesses bulbar symptoms, fine and gross motor function, respiratory symptoms, and the need for ventilation or feeding tubes. You can access the scale here. In clinical trials, changes in ALSFRS‑R scores are often used to evaluate whether a treatment may slow functional decline, with higher scores indicating better function and smaller declines suggesting slower disease progression. However, ALS progression varies widely from person to person, and the scale may not capture all aspects of the disease equally. For this reason, ALSFRS‑R results are commonly used alongside other clinical and biological measures and must be interpreted with care.
** 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 stabilize or plateau as the disease progresses, and when a substantial drop occurs with treatment, often around 30%, it is considered meaningful. Reductions of less than 30% are difficult to reliably attribute to an effect of the treatment.
In our March update, we covered results reported from this Phase 2 trial. Since then, an additional report has been released. The trial investigated the therapy in both participants living with SOD1-ALS and participants without a known genetic cause.
The company states that new findings provide evidence of clinically meaningful disease modification that tracks directly with prolonged survival, supported by reductions in neurofilament light chain (NfL) in blood and phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid after six months of treatment. Based on data shared across multiple public presentations, these findings remain very preliminary. Additional measures mentioned, such as disease stabilization and reduced functional decline measured by the ALSFRS‑R in SOD1 subgroups, should also be viewed with caution due to the small number of participants and the fact that the data does not yet show clear or consistent changes.
It is important to emphasize that small Phase 2 studies are not designed to demonstrate efficacy. Findings from Phase 1 or 2 trials should be understood as early signals rather than evidence of a confirmed treatment effect and are often too limited to provide clear indications of benefit.
Larger, well‑designed trials will be required to determine whether AP‑101 provides any benefit for people living with ALS.
A new publication highlights Phase 2 data from the PARADIGM trial, investigating PrimeC. This trial was able to recruit 68 participants living with ALS, who were randomized in a 2:1 ratio to receive PrimeC or placebo for six months, followed by another six months of open label extension (where all got the experimental drug). In the end, 29 participants completed the open label phase, as some decided not to proceed, or were unable due to death, disease progression, or other reasons.
Safety: The primary outcome of the study was safety, which was met. The most common side effects reported included gastrointestinal symptoms, as well as headaches, fainting, and mildly elevated blood pressure. Importantly, no treatment‑related deaths or life‑threatening events were observed.
ALSFRS‑R: During the six‑month randomized portion of the study, participants receiving PrimeC had higher ALSFRS‑R* scores than those on placebo, with a mean difference of 2.23 points after six months. In the open‑label extension, participants who started on PrimeC had a 7.92‑point difference at 18 months compared with participants originally assigned to placebo. While these results may seem intriguing, it is important to interpret ALSFRS-R results from any clinical trial of this size with care. Differences between groups can arise for a number of reasons unrelated to treatment, including natural variation in disease progression, imbalances between small groups at the start of a study, and the effects of chance or participant drop-out. Larger, well‑designed trials are needed to account for these factors.
Neurofilament light chain (NfL): At six months, NfL levels were very similar between the two groups. Participants receiving PrimeC had NfL levels that were about 0.8% lower than those receiving placebo. By month 18 in the open‑label phase, participants originally assigned to PrimeC had approximately 9.4% lower NfL levels compared with those originally assigned to placebo.
Although a reduction was seen, a meaningful reduction in NfL is generally considered to be much larger, often around a 30% decrease, and NfL levels are also known to stabilize as the disease progresses. These results are another reason to consider the seemingly positive ALSFRS-R data with caution.
Target engagement biomarkers: In addition to functional measures, the PrimeC trial also examined biological markers to assess whether the drug was having its intended effects in the body. These included iron regulatory proteins and circulating microRNAs. Researchers observed changes in these markers with PrimeC treatment, suggesting the drug was influencing the biological processes it was designed to target, a concept known as target engagement. However, we still don’t know if targeting these biological processes influence disease.
Based on these clinical and biomarker findings, NeuroSense plans to advance to a confirmatory Phase 3 trial. A well-designed Phase 3 study will be important to better understand whether PrimeC may provide benefit. At present, however, there is not enough evidence to conclude that it is effective.
It is unknown at this time if Canadian sites would be involved in the Phase 3 trial. Our clinical trials database will be updated once we receive more information.
On April 21, Ractigen Therapeutics, a company based in China, shared early results from a Phase I study of RAG‑17. The study included 20 participants who received different dose levels of RAG‑17. Participants randomized to receive the treatment or placebo in a 3:1 ratio.
The study reported an 81% reduction in NfL following a single dose, along with a favourable safety profile, however, no further detailed data was provided to be analyzed. The company also states that early signals of clinical stabilization were also observed at the highest dose level, though the findings are preliminary.
It is important to emphasize that as a Phase 1 study, the primary goal was to assess safety and biological activity, and further research in larger, later stage trials are needed to determine whether these biomarker changes translate into meaningful benefits for people living with SOD1‑ALS. A Phase 2 trial for the study has already started in China.
*The ENCALS survival prediction model is a research tool that estimates how ALS may progress in an individual based on data from more than 11,000 people living with ALS across Europe. It combines factors, such as age at onset, disease progression rate, breathing function, and site of symptom onset to predict expected survival. Researchers often use the model to provide context, comparing what was expected to happen with what was actually observed in clinical studies, but it cannot predict outcomes perfectly for any one person.
On April 20, AB Science announced a new preprint publication reporting additional analyses from the Phase 2/3 AB10015 trial, which investigated masitinib in ALS, as an add-on to riluzole. Previous ALS clinical trials investigating masitinib provided inconclusive results to date.
In this new analysis, researchers looked at long-term survivors treated with masitinib, comparing their disease progression against historical data and the ENCALS survival prediction model*. The data primarily suggests that the trial participants treated with 4.5 mg/kg/day have a better five-year survival rate and better than expected independence. This manuscript extends from a previous survival study and other post hoc analyses (looking for trends in data after a trial has ended, and susceptible to bias) that have limitations preventing firm conclusions to be made about any benefit of masitinib. AB Science has attempted to use data from this study that ended in 2017 to achieve approval in Europe and Canada but has not been successful to date. It is also important to emphasize that any publication labeled as a preprint (often published on sites called bioRxiv or medRxiv) are not yet peer reviewed.
A new Phase 3 trial of masitinib in ALS is currently ongoing, and it aims to recruit more than 400 participants with moderate disease progression in the U.S and Europe.
On April 30, Corcept Therapeutics shared updated results from the Phase 2 DAZALS study that enrolled 249 people living with ALS. Participants were randomized to receive either a low dose (150 mg), high dose (300 mg) of the dazucorilant, or placebo daily for six months. An open‑label extension followed where all participants were given the option to receive the 300 mg dose.
The primary goal of the trial was to slow functional decline, measured using the ALSFRS‑R*. This primary endpoint was not met, meaning dazucorilant did not significantly slow loss of function over the initial six months (24 weeks) study period.
Despite this, Corcept reported exploratory survival findings from secondary analyses. In the main survival analysis, researchers compared people originally assigned to the higher dose of dazucorilant with those who received placebo and did not continue to the open–label extension. During the initial six-month study period, there were no deaths in the high dose group (0/83) compared with five deaths in the placebo group (5/82). Other clinical trials have also reported no deaths in the treatment group over six months, so this finding should not be viewed as confirming a benefit.
With longer follow–up, people who started on the higher dose were reported to have a lower risk of death at two years when compared to those who were on placebo and chose not to move to the 300 mg open label extension phase. Several factors make this finding more difficult to interpret, including the limited information on why a small group of participants (18 of 83 who began on placebo and did not continue) chose not to move forward with the active treatment. For example, if discontinuation was related to disease progression, this could influence the survival analysis.
In a second exploratory analysis, another very specific subgrouping was reported as demonstrating a lower risk of death for early and continued treatment with higher dose dazucorilant. Although these analyses may seem notable, they reflect only selected, restrictive ways of interpreting the data, and it is not clear whether other analyses may have showed different results. At this stage, these findings are most relevant for informing investor interest. Based on what is known about the ALSFRS‑R, a longer, placebo‑controlled study period will likely be needed to determine whether dazucorilant provides meaningful benefit for people living with ALS.
Corcept has indicated plans to advance dazucorilant into a Phase 3 trial to further evaluate its safety and effectiveness. Canadian sites will hopefully be involved in the Phase 3 trial, and our clinical trials database would be updated should we receive this information.
In April 2026, Shionogi announced that it has acquired the global rights to RADICAVA (edaravone) from Tanabe Pharma. According to the company, this will not affect access to the medication for people living with ALS.
A faster, more accurate ALS diagnosis is difficult because many changes in the body can look similar across different conditions, and there is still no single test that can clearly diagnose ALS. This is why researchers are currently studying ALS diagnostic biomarkers, which are measurable signals in the body (such as proteins found in blood) that can help provide additional clues in identifying ALS early on. One biomarker that has gained significant attention in ALS research is neurofilament light chain (NfL), a protein released into the blood when neurons are damaged. NfL is already being used as a prognostic biomarker* at the group level, particularly in clinical trials. However, work is ongoing to understand how NfL can be meaningfully interpreted at the individual level, especially during the diagnostic process.
Importantly, elevated NfL levels are not specific to ALS, which is why NfL cannot be used as a standalone diagnostic test for the disease. However, it may still add value to the diagnostic process, as shown in this study by researchers at Washington University School of Medicine. In this research, they examined whether measuring blood NfL could help strengthen diagnostic confidence at an earlier, more uncertain stage of disease. Focusing on people who received a provisional ALS diagnosis at their first clinic visit, they found that those who later progressed to a definite ALS diagnosis were more likely to already have elevated NfL levels. When NfL measurements were combined with existing clinical guidelines, clinicians were better able to identify individuals likely to progress to ALS than when using clinical criteria alone.
The study reinforces that when used together, biomarkers and clinical assessments may reduce diagnostic uncertainty, help people access appropriate care sooner, and support earlier entry into clinical trials. Already, NfL is also being used as a predictor of disease onset in the first-ever presymptomatic ALS clinical trial, ATLAS.
There is also interest in whether NfL could be collected earlier in the referral process, serving as an early signal of nerve cell damage to help general practitioners recognize when to refer someone to a neurologist sooner, expediting the diagnosis process from the beginning.
While larger studies are still needed, this research adds to growing evidence that NfL is a valuable biomarker in ALS, with many of its possible uses still being explored.
*For more information on biomarkers and ALS, read our Inside the Science on the topic.
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