Headline result:

The EXPERTS-ALS study has found that Ropinirole does not lower neurofilament light chain levels in the blood. As a result, we will now stop entering new participants onto the Ropinirole arm of the study. 

We explain what this means for the trial and the wider MND/ALS community below.

What is EXPERTS-ALS?

EXPERTS-ALS is a research study designed to screen drugs rapidly for their potential to slow the progression of ALS. Supported by a group of leading scientists, we select drugs to test for changes in a blood test marker called neurofilament light chain.

• Lower neurofilament levels are linked to a slower rate of disability progression in people with ALS. 

EXPERTS-ALS is not designed to prove whether a drug provides clinical benefit to people living with ALS, defined as how someone feels, functions or survives. It can only look for an early signal of disease-slowing. It aims to quickly identify the most promising drugs to go forward into the larger clinical trials needed to test this (phase 3 trials). When we do identify a drug which results in a large and important reduction in neurofilament levels and potentially slowing ALS progression, we will recommend that it is prioritised for clinical benefit testing in a phase 3 trial.

What is an interim analysis?

An interim analysis is when the results are reviewed during the study whilst participants are still taking the study drugs.

When an interim analysis shows that a drug does not appear to be statistically lowering neurofilament levels, we stop testing it in new participants. It does not mean that the stopped drugs have caused any harm. These decisions follow strict guidelines agreed upon by a group of expert doctors and researchers before the study started. 

What were the results for Ropinirole?

An independent group of doctors and statisticians has reviewed the data collected so far, which has been analysed using an innovative statistical model. 

The results showed that the neurofilament level for Ropinirole has not changed. This means that the drug does not meaningfully slow down the disease process in MND/ALS. The independent oversight group recommended that we stop testing this drug in new participants.

Who was included in the analysis?

• 42 participants were treated with Ropinirole. 

• 22 participants provided the blood samples at week 18 used for the analysis.

What does this mean for individuals? 

Participants who are currently taking ropinirole will stop taking the drug, either immediately following a short tapering period, or at their next study visit. This allows us to gather all of the data and check for the possibility that some participant neurofilament levels have responded differently to others. It is important to say that the stopping of a drug arm in this type of analysis is not because of safety issues. There is no evidence that either drug has caused harm.

The results do not affect the treatment of participants currently taking one of the other study drugs.

What does this mean for the study?

We understand that it may be disappointing to hear that ropinirole does not lower neurofilament levels. However, this is an important milestone for EXPERTS-ALS and the data collected from the participants are still extremely useful to advance knowledge. It also shows that the study design is working as intended, allowing us to quickly decide which drugs are unlikely to lower neurofilament levels. 

What happens next?

We will write up the full results to publish them in a medical journal and share a summary on our website.

EXPERTS-ALS remains open and active. Current participants will remain in the study and we are continuing to recruit new participants to the following drugs: doxycycline and salbutamol.

We also have an expert panel of doctors and scientists identifying new drugs to be included in the study. In future, this is likely to include novel compounds as well as repurposed drugs (drugs which are already used to treat other conditions). 

Thank you

We are grateful to all of the participants who have generously given their time to take part in this study. We cannot advance the road to effective treatment without them and thank them on behalf of all those living with MND/ALS. 

None of this can be done without the dedication of those living with ALS and those who support them, who give their time to push the boundary towards success for everyone. The study is funded by a partnership between the UKRI Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR), with support from the Motor Neurone Disease Association, My Name’5 Doddie Foundation and LifeArc, with the Darby Rimmer Foundation joining soon. We are thrilled at the successful involvement of so many centres across the UK in EXPERTS-ALS, many new to the field, as part of the shared desire to build capacity in ALS trials. The skilful coordination of so many moving parts by the Sheffield Clinical Trials Unit, Sheffield Teaching Hospitals NHS Foundation Trust and Sheffield Biomedical Research Centre, for a trial with no prior off-the-shelf blueprint has been extraordinary. It is coupled to the precision of the setup and delivery of what is the first dedicated NFL laboratory for an ALS trial, with a novel Bayesian statistical analysis pioneered by colleagues at Oxford University. EXPERTS-ALS is a world-leading initiative that the UK ALS research community can all feel proud to be a part of.