An interim result from the EXPERTS-ALS trial shows neither drug lowered a key marker of MND progression, a fast, clear answer that lets researchers focus resources on more promising candidates.

EXPERTS-ALS, the UK’s platform trial for rapidly screening potential MND treatments, has found that metformin and nifedipine do not lower neurofilament light chain (NfL), a blood marker linked to how quickly the disease progresses. Recruitment to the metformin and nifedipine arm has now stopped. Three other drugs, ropinirole, doxycycline and salbutamol, remain in active testing.

EXPERTS-ALS is designed to answer this kind of question in months rather than years, using changes in NfL as an early signal of whether a drug is worth taking forward into a full-scale phase 3 trial. 36 participants took metformin and 31 took nifedipine, each for up to 24 weeks before this analysis, far fewer, and far faster, than a traditional trial would need to reach a comparable answer.

“The quick rejection of metformin and nifedipine is what our community needs. Yes, we would have rather seen a quick identification of a positive hint, but not spending three years, with placebo, is exactly what research needs. Screen, discard, and move on. Speed.” — Lee Millard, EXPERTS-ALS Patient Representative

What this means for participants

For people living with MND, this result means fewer people will spend months on a drug that’s unlikely to help, and more focus goes to drugs with a real chance of slowing the disease. There is no evidence that either drug has caused harm; they simply didn’t produce the biological signal EXPERTS-ALS is designed to detect. Their data remains a valuable part of the study.

What this means for the platform

The trial’s Chief Investigators describe the result as exceeding their expectations for how the platform would perform at this stage, an early validation of EXPERTS-ALS’s design. With relatively few participants and a matter of months, the platform was able to reach a clear answer using a novel Bayesian statistical approach pioneered with colleagues at Oxford, instead of the hundreds of participants and years a conventional trial would need.

This result does not mean metformin or nifedipine are unsafe, or that they could never help someone with MND,  EXPERTS-ALS is a screening step, not a test of clinical benefit. It shows only that neither drug produced enough change in this specific marker, in this study, to justify continuing to test it here. A positive NfL result would not have proven a drug works either, it would simply have earned a place in a larger phase 3 trial to test that properly.

What happens next

This result was only possible because of the participants who volunteered their time and gave blood samples throughout the study, and the clinical teams and patient representatives who support EXPERTS-ALS across its sites. With thanks to LifeArc, the MND Association and My Name’5 Doddie Foundation.

Read the full results summary, or read more about how this moves our wider work forward.

In more depth

Full data: metformin — 36 participants treated, 22 provided week 18 blood samples used in the analysis, 5 stopped treatment before week 18 (data retained). Nifedipine — 31 participants treated, 18 provided week 18 samples, 1 stopped before week 18 (data retained).

The analysis was reviewed by an independent oversight group of doctors and statisticians against a pre-specified statistical analysis plan, using a Bayesian statistical model developed with Oxford University colleagues. EXPERTS-ALS is coordinated by the Sheffield Clinical Trials Unit, Sheffield Teaching Hospitals NHS Foundation Trust and Sheffield BRC, with a dedicated NfL laboratory believed to be the first of its kind for an ALS trial.

EXPERTS-ALS continues to recruit to its remaining drug arms, ropinirole, doxycycline and salbutamol, and an expert panel is identifying further candidate drugs, including novel compounds as well as repurposed ones, for future arms.

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