The long-awaited results from the MIROCALS clinical trial investigating low-dose interleukin-2 (IL-2) for motor neurone disease (MND) have been published in The Lancet, revealing a complex picture of the drug's efficacy in this devastating neurological condition.
Trial Results Show Mixed Outcomes
The MIROCALS (Modifying Immune Response and Outcomes in ALS) trial, which tested an existing drug called IL-2 in people with MND, failed to meet its primary endpoint of demonstrating efficacy across the entire study population. When analyzing all participants, the treatment showed a modest 12% increase in survival for those receiving IL-2 compared to placebo, but this difference did not reach statistical significance.
However, a pre-specified subgroup analysis revealed potentially important findings. Researchers identified that patients with lower levels of neurofilament—a biomarker associated with slower disease progression—appeared to benefit from the treatment. In this subgroup, those receiving IL-2 were 18% more likely to be alive at the end of the trial compared to those on placebo with similar neurofilament levels.
Additionally, the researchers reported a 23% decrease in the rate of change in the ALSFRS-R score (the standard functional rating scale for MND) between IL-2-treated patients with low neurofilament levels compared to similar patients receiving placebo.
Biomarker-Guided Treatment Approach
The findings suggest a potential shift toward biomarker-guided treatment approaches in MND, where therapy selection might be tailored based on specific disease characteristics rather than applying a one-size-fits-all approach.
"These results indicate that IL-2 is not an effective treatment for all people with MND, but that it may have a modest benefit for some people with MND who have slower disease progression, as measured by levels of neurofilament," noted the research team in their publication.
Dr. Gilbert Bensimon, Principal Investigator of the MIROCALS trial, commented: "While we are disappointed that IL-2 did not demonstrate significant benefit across the entire study population, the subgroup findings provide important insights into potential treatment strategies for specific patient populations. This highlights the heterogeneity of MND and the need for personalized approaches to therapy."
Expert Evaluation Underway
Given the complexity of the findings, the MND Association, MND Scotland, and My Name's Doddie Foundation are awaiting guidance from the UK MND Clinical Studies Group (CSG), which includes leading neurologists, researchers, and people with MND.
"We understand the urgency of this, and that people with MND have already waited too long for these results. So we have asked the CSG to come to a view on this in the next few days. What we do next will be led by this expert view," stated the MND Association.
The three organizations are collaboratively pursuing all available avenues to make proven treatments available to people with MND as quickly as possible and on an equitable basis.
Understanding IL-2 and Its Mechanism
IL-2 is an immunomodulatory drug that regulates the activity of certain immune cells. In MND, where neuroinflammation is believed to contribute to disease progression, low-dose IL-2 was hypothesized to help regulate the immune response and potentially slow disease advancement.
The drug has been used at higher doses for other conditions, including certain cancers, but the MIROCALS trial specifically investigated whether low doses could provide benefit in MND while minimizing side effects.
Patient Community Response
The publication of these results comes after significant anticipation within the MND community. Many patients and advocates have expressed frustration about the time taken for the full results to be published, following the announcement of preliminary findings in December 2022.
"We have shared the frustration in the MND community about how long it has taken for these results to be published so this is a welcome step forward," acknowledged the MND Association in their statement.
Implications for Future Research
The MIROCALS findings contribute to a growing body of evidence suggesting that MND is not a single disease but rather a spectrum of conditions that may respond differently to various treatments. This has important implications for future clinical trial design and drug development strategies.
The identification of neurofilament as a potential predictive biomarker for treatment response aligns with recent research highlighting its importance in MND. A March 2025 study from scientists in San Francisco suggested that neurofilament light chain (NfL) may play a direct role in disease progression by triggering inflammation in the brain through activation of microglia cells.
Next Steps
As the MND community awaits guidance from the Clinical Studies Group, questions remain about whether further trials focusing specifically on patients with lower neurofilament levels might be warranted, or whether there could be a path forward for IL-2 as a treatment option for a subset of MND patients.
The three MND organizations have emphasized their commitment to pursuing all available avenues to make proven treatments accessible to patients as quickly as possible, recognizing the urgent need for effective therapies in this rapidly progressive and fatal condition.
