Alternate title – The journey to a treatment reaching patients after a proven efficacy indication.

Well it’s certainly not my snappiest opening statement for a post on MND/ALS folks!? Today’s short narrative is all about the real world procedures which are required to:

….get a new treatment into our community, once, and only once, solid, data driven, signs of effectiveness have been shown.

It is often imagined that once a drug has shown effectiveness, and perhaps even approved in one part of the world, that it would simply become immediately available globally. Today, I will try to put some perspective on why this is often not as clear cut as it may appear. But, just why I am writing this article now?

We are in an interesting time for MND research with several ‘promising’ drugs in trials. We do have to, however, keep continuing referring to these avenues as promising, for anything can happen before any one can cross over the line, or not.

More specifically, the road I drive along today is for our community here in the UK. Different systems do exist globally, and although most of my description will still largely probably apply, there are most certainly national nuances.

To end this nervous, and to be honest, quite bumbling introduction, I am going to make one small, but significant statement. This might just be the single biggest difference since the era in which the only globally approved effective disease altering drug, Riluzole, was discovered over 25 years ago. This could have a strong positive effect on future approval processes.

The world is now effectively a tiny planet with instant communications. Whether emanating from the USA, the UK or Australia, good or bad news travels at light speed.


Ok, let’s start out on the path to regulatory approval and to what is often seen and perceived purely as only “red” tape.

In 2020, because of our “unmet need”, that is quite unlike no other disease on this earth, there would be pressure to speed any potential game changing treatment to market and into the bodies of patients. In the UK, the MND Association along with consultants, researchers, other MND charities and, above all, those living with MND/ALS, would work together, to move with tempered immediacy.

But, what are the quantifiable steps on that road, and is there any flexibility in the apparently unfathomable processes?

The first stone will be laid in the ground when the MHRA(Medicines and Healthcare regulatory agency) or the EMA(European Medicines Agency) receive into their inboxes an application from the treatment developing company to market a new drug or treatment in the UK. They would be presented with, and will analyse, the entirety of evidence from clinical trials.

This very act of a timely submission itself would be a strong indicator of the potential eventual success of a treatment. Does the drug company even commit resources and finances to apply to the UK and/or European market?

Some of us might recall the promise of a second disease altering drug that appeared back in 2017. Radicava, was eventually approved in the USA but was never marketed here or anywhere else in Europe. Why? Perhaps the sponsoring company may have felt that the UK and European regulations would have required additional validation of effect? Our local community has not raised the pressure to pursue the company and no such request has ever been received. My personal opinion, regarding this drug, is that we haven’t actually missed out on much. It certainly does not raise any UK ‘buzz’ or discussion.

I do digress somewhat. Returning to our prospective journey. After the receipt of the request, a comprehensive scientific assessment will be undertaken. This would typically be supported with the results of at least one Phase 3 trial having achieved its primary aim, or multiple significant sized Phase 2 trials showing some repeatable and solid efficacy signals.

If the threshold for approval is judged reached, the treatment would then be granted a licence, which would allow marketing in the UK. This piece of paper is only the start of the journey, however.

The next critical step, which might run in parallel to the formal approval, involves our marvellous NHS, and is the most important stage of the journey. Here in the UK there is a healthcare system that is free for all at the point of entry. It most certainly isn’t perfect, but it’s darn near! The NHS, to put in transatlantic language, is effectively a ‘single payer system’, and that being our government, funded purely by public taxes.


Put simply, any drug manufacturer negotiates with ONE and only ONE buyer within a country of our nation. This provides a solid foundation for price regulation and control. These discussions can be complex, and in England, NICE are the responsible authority for assessing new drugs, including their value for money, patient burden, quality of life improvement etc.

This will be the moment in time when those of us who are affected by MND/ALS could and might exert a huge influence. There are no truly effective treatments currently, and any new drug could be life changing for many of us. I would expect a campaign, involving patients and the MND Charities to ensue, especially if the treatment is considered significantly game changing.

Although pricing negotiations are obviously confidential, one historical drug agreement, not for MND but for Multiple Myeloma, is worth noting for being both very simple and at the same time very effective for the buyer and the supplier, ie a win/win.

The UK government pricing agreement for Velcade for Multiple Myeloma back in 2007 specified that the pharmaceutical company would only be paid by the NHS for patients who responded ‘well’ to the drug! How simple is that? The agreement was kept, and significantly reduced the price for a pioneering drug. This is the kind of a no-brainer give/take that can be reached, especially if the company is confident of a positive effect in due course, despite perhaps insufficient compelling evidence at the time of application.

Are we there yet!?

Not quite.

Straddling the licence application and price negotiations is the simple matter of the logistics of treatment production, deployment plans, patient selection and drug administration.

I am, of course, saying this rather with my tongue firmly in my cheek! This process could vary, from the simple re-purposing of an existing drug through to the extremely complex scenario of a personalised, high burden invasive new treatment requiring, perhaps, even the building of new physical facilities to manufacture.

In summary. Although the processes seem complicated and are often portrayed as inflexible, they are this way because drugs have to be effective, and there are wide societal concerns that need to be reflected. You might find some of the discussion interesting in these selected ethics reports. Our NHS with its limited funding has to receive value for money, despite our severe plight. History has also shown that short cuts can be disastrous, and slow eventual effective treatments. Take a look at the the background on the Cancer Drugs Fund (CDF) here in the UK. Is it an example of ‘On the face of it’ good intent but leading to ethically questionable results and unintended financial consequences? I’ll let you be the judge. The subject of health economics is most certainly not a simple conundrum.

Concluding this brief section on economics, it may come as a surprise to my readers in the USA that here in the UK, private insurance companies will not typically pay for an effective treatment if it has not been approved for all by our NHS! So unless you have access to considerable funds outside of insurance cover, access to drugs not used by the NHS, despite any efficacy, would be truly only for the privileged few.

I will now finish today’s post with a couple of important potential short cuts to approval.

1 – Conditional Approval

Conditional approval is an excellent pathway to drug approval, beneficial for the regulatory body, the drug developing company and patients. The EMA published Guidelines describe the criteria for this pathway to be considered. However, they can be succinctly summarised as:

  • The prospective treatment for a disease for which there is currently an unmet need – MND/ALS is most certainly that! ✅
  • The benefits must outweigh the risks to both patients and public health. 
  • Although the current evidence is not comprehensive, the sponsor is likely to be able to supply the data in a reasonable future timeframe that could prove efficacy.

If a drug is then granted such a conditional approval, the company is legally entitled to market in Europe. However, the approval is reviewed annually and strictly subject to any additional agreed obligations deemed necessary, such as further trials.

Note: this pathway does not yet exist in the USA. However, there is a current bill (HR7269) that could well create something similar, but not entirely comparable.

2 – Early Access Scheme (EAMS)

EAMS is very similar to conditional approval and is a potential powerful rapid cut through method. Although sounding very attractive to patients on first read, there is one crucial difference, and that is the drug must be supplied totally free by the company. This, on the face of it, might only favour a large pharmaceutical company who could fund such a scheme for year or more before full approval. But still this pathway could be very useful.

Please note that both of these short cuts still retain a ‘bar’ of both technical and scientific rigour that must be hurdled. The detail of this is beyond this short post, but my series on the Devil is in the Detail might help you traverse and understand the need for this often perceived bureaucracy.

I hope you have found today’s article useful, perhaps bringing some clarity to a daunting process here in the UK. It is not as simple as first envisaged, but it is designed to protect us, and above all be science led.

And finally, please be encouraged by today’s post and to reenforce this, please revisit the introductory paragraphs of this post and also the very latest Dodcast (from Doddie Weir’s MND Foundation featuring Professor Ammar Al-Chalabi) for why today is a good time to pounce on this disease which will hit 1 in 300 of us, even despite COVID.