First results emerging from MIROCALS, a clinical trial of interleukin-2 in MND
09 January 2023
09 January 2023
Top-line results from the MIROCALS (Modifying Immune Response and OutComes in ALS) clinical trial were presented today, the opening day of the Motor Neurone Disease Association’s 33rd International Symposium on ALS/MND. The results were presented by Dr Gilbert Bensimon, Centre Hospitalier Universitaire de Nîmes.
The MIROCALS clinical trial is a phase 2b trial of low-dose interleukin-2 (IL-2), which regulates the immune system by increasing the number of specialist immune cells called regulatory T cells (T-regs). In many people with MND, the number of T-regs is significantly reduced, which can lead to overactivation of the immune system and accidental damage to the motor neurons.
The trial recruited participants from 17 sites in the UK and France. Participants were recruited soon after receiving an MND diagnosis, and treated with riluzole (currently the only approved treatment for MND in the UK), for 3 months. After this period, half the participants received IL-2 and the other half received placebo (dummy drug) for 18 months.
Overall, the trial results indicated a modest but not statistically significant decrease in the risk of death after 21 months in those people receiving the active drug. However, when the researchers looked at how individuals responded to the treatment, they found that some people responded better than others.
Researchers grouped participants by the level of a specific biomarker found in their cerebrospinal fluid (CSF), at the start of the trial.The biomarker, ‘phosphorylated neurofilament heavy chain’ (pNFH), is released into the CSF when motor neurons become damaged. People with high levels of pNFH in their CSF shortly after diagnosis tend to have more aggressive and rapidly progressing disease, compared to those with low or moderate levels. The trial data show that, in people who had rapidly progressing disease and high pNFH levels at the start of the trial, no significant treatment effect could be detected. In contrast, in people who had low to moderate pNFH levels, there was a significant decrease in the risk of death after 21 months, of over 40%.
The results suggest that IL-2 could be an effective treatment for a sub-group of people with MND, with a certain level of pNHF at diagnosis. While the idea that some treatments may only benefit a sub-group of people with MND is not new (see tofersen for people with SOD1-MND and lithium carbonate for people with a specific variant of the UNC13A gene as examples), it is a novel approach to identify which people may respond to a treatment best based on a measurable biomarker instead of genetic make-up.
Professor Nigel Leigh, co-lead and chief trial investigator, Brighton and Sussex Medical School, said “A key strength of MIROCALS has been the collaboration of leading European research groups in immunology, biomarker development and genomics. There remain many questions to address, but the wealth of data and samples accumulated are supporting ongoing research to better understand the factors that drive ALS [MND] disease progression. These will hopefully open the door to new therapeutic avenues and more personalised approaches to treatment, to deliver even more positive outcomes in future trials.”
Jessica Lee, Director of Research at My Name’5 Doddie Foundation, said “Although further research is needed, the initial results of MIROCALS indicate that modifying the immune system could be a viable treatment strategy to alter the progression of MND. MIROCALS collected numerous blood and CSF samples from each participant and has created a valuable resource that should help us to accelerate this and other potential immune-modifying treatments to the clinic. We are proud to be supporting three projects in the UK and Italy which are analysing these samples to improve our understanding of the biological effect of IL-2 and answer the question about why it slowed disease progression in some people, but not others.”
We would like to thank the many people with MND who took part in the MIROCALS trial; their donation of samples has contributed to this advancement in our understanding of the role of the immune system and MND and, we hope, will lead to new treatments for MND. We extend our thanks to our wonderful supporters, without whom we would not be able to support this important work.
To find out more about one of the projects we are funding, read about our recent visit with Professor Tim Tree here.
To find out more about the MIROCALS consortium, visit the MND Association’s web page here.
Can people with MND access IL-2?
Currently, IL-2 is not licensed to treat MND. It is only licensed to treat a small number of rare cancers. The dosage used to treat those cancers is much higher than that which was tested in the MIROCALS trial for MND.
The researchers will discuss the data with drug regulatory agencies to understand whether another clinical trial will be required before the drug could be added to the ‘tool kit’ of therapeutic options available to people with MND.
We will keep you updated on the latest developments, but if you want further information about IL-2 in the meantime, please speak to your consultant.