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Scientists welcome results from trial investigating Interleukin-2 in MND patients



Researchers have shown “top-line” results from the phase 2b trial of low dose Interleukin-2 (ld IL2) in MND patients.

The MIROCALS (Modifying Immune Response and Outcomes in ALS) Trial Consortium has announced the findings at an online audience by Dr Gilbert Bensimon, Centre Hospitalier Universitaire de Nîmes, on the opening day of the 33rd International Symposium on ALS/MND, organised by the Motor Neurone Disease Association.

The MIROCALS trial, conducted in clinics across France and UK, in collaboration with eight research groups, tested whether low doses of IL2 can alter aspects of the immune system associated with inflammation in the central nervous system, which is believed to play an important role in the speed at which MND, also known as ALS, progresses.

Following a 12-week run in period while starting treatment with riluzole – the accepted standard drug treatment – a total of 220 people with MND attending 17 specialist clinics in the UK and France were randomised in equal proportion to receive subcutaneous injections of low-dose interleukin-2 or placebo for a period of 18 months, with the primary outcome to demonstrate a treatment-related decrease in the rate of death.

The treatment was well tolerated, with adverse events recorded as mostly mild to moderate, occurring across both active treatment and placebo arms.

The primary core biomarker (CSF pNFH) revealed a highly significant association between CSF pNFH levels and survival.

Furthermore, pre-planned analysis of efficacy adjusted on the level of CSF pNFH at randomisation showed a significant effect in favour of IL2 on disease progression and survival.

CSF pNFH measurements were critical in the context of developing a “personalised medicine approach” by defining groups of participants with different responses to IL2.

According to CSF pNFH levels, in about 20 per cent of the population no significant treatment effect could be detected in these rapidly progressive patients all with high CSF pNFH levels.

However, 80 per cent of the population had low to moderate CSF pNFH levels, correlating with less aggressive disease progression and for these patients there was a significant decrease in the risk of death of over 40 per cent.

Dr Gilbert Bensimon, lead investigator and project co-ordinator, Centre Hospitalier Universitaire de Nîmes (CHU), said: “While the primary unadjusted survival analysis was not significant, the pre-planned adjusted analysis – an approach recommended by the US FDA – shows a positive effect of IL2 on survival.

“Furthermore, a joint rank analysis of survival and function also showed significant benefit with IL2 compared to placebo.

“These results indicate that IL2 does have a beneficial effect in ALS, but clearly further studies are needed to see if this effect can be enhanced by different treatment schedules and by exploiting the insights we have gained by integrating CSF pNFH and other biomarkers into the trial design.”

He added: “Peripheral changes in immune processes and their knock-on impact on central neuroinflammation have emerged as exciting targets for therapy development.

“MIROCALS is the first large scale randomised placebo-controlled trial to demonstrate “proof of principle” in relation to IL2 with the potential to translate into clinical benefit for people living with this devastating condition.”

Professor Nigel Leigh, co-lead and chief trial investigator, of 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 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.”

Dr Brian Dickie, director of research for the UK-based MND Association, said: “ALS is a relentlessly progressive and devastating disease that robs people of their independence and ultimately their lives.

“Taking part in clinical trials requires a significant commitment from people with ALS and we are so grateful of everyone who volunteered for this important and ground-breaking study.”