EXPERTS-ALS Accelerating MND Drug Development

You may have seen the recent news from the UK MND Research Institute announcing that one of its first projects, EXPERTS-ALS, funded by the NIHR from the £50m successful UK government United2endMND campaign, and supported by the leading UK MND charities, is now operational.

EXPERTS-ALS is a new drug ‘screening’ platform. It will be run out of 11 MND centres in the UK. It aims to assist breaking the stream of failed MND trials seen globally for many years. The platform provides greater insight into candidate drugs that aims to help ensure only the very best human trials.

The road to bringing new treatments to patients, for all diseases, is long and complex. This journey is certainly very frustrating for us living with MND. Our leading charities in the UK have recently published some useful information on the process. In this short post, we try to show how EXPERTS-ALS fits into this bigger picture.

In the first in human trials, so called phase 1 studies, the focus is necessarily on that critical initial safety of a candidate drug. These are small, perhaps 5 to 10 patients, experiments that look for adverse events, examine appropriate dosage and aim to conclude whether further investigation is safe.

It is not until the second stage, a phase 2 trial, which is far larger, often typically 200 patients, is it possible to ‘start’ to assess efficacy, ie whether a candidate drug is changing the path of our disease for the better.

History has shown that phase 2s and their associated subsequent phase 3s (the definitive and vital efficacy trial(s)) are incredibly expensive and sadly the majority of phase 2s have also been long and inconclusive, contributing to, perhaps, the inevitable, ‘unbearably’ high subsequent failure rate of phase 3s.

So it can be said, perhaps, that there is an urgent need to reduce time in phase 2s and to run less, but more likely to succeed, phase 3s. A successful phase 3 is what we all want to see.

We are convinced that this is an ambition that our whole community would welcome and get behind. But how could this be achieved? What does EXPERTS-ALS bring to the game?

EXPERTS-ALS is an attempt to make a real inroad into this ambition and can effectively be considered as a phase 2 platform. It has the potential to become a reusable service that may be used/sought after by Pharma not only in the UK but globally. Pharma want to know as soon as possible, just like we do, if a treatment works or not. They would want to move on to the next candidate drug and not sit in endless trials, expending both valuable resources and money.

By using innovative statistical modeling, over a maximum of 6 months, EXPERTS-ALS will look for a single measure ‘hint’ of potential effectiveness, that of lowered NfL (a biomarker). Combine this with less than 75 patients per candidate drug with no placebo, EXPERTS-ALS could reduce phase 2 time burden and help validate whether a phase 3 should be considered.

After a drug candidate has completed a successful phase 1, EXPERTS-ALS could potentially save some Pharma vital money and resource by removing a lot of the infrastructure costs of a phase 2. EXPERTS-ALS provides an alternative option for drug candidates after that essential phase 1. A Pharma may still choose to plan a customised phase 2, but EXPERTS-ALS might be worthy of consideration.

EXPERTS-ALS will be ‘open to enquiries’ to all safe candidate drugs including, for example, new compounds, repurposed and repositioned drugs.

The EXPERTS-ALS funding proposal was internationally peer reviewed and is funded by the UK government and the UK MND charities.

We will continue to update the community on the progress of this project. We encourage patients and families to follow the activities of the UK MND Research Institute.

Finally, you might find this video discussion made by Professor Martin Turner and Professor Chris McDermott, the study leaders of EXPERTS-ALS, a useful watch.

United2EndMND