Is the Mirocals Consortium taking the fastest route for patients to access low-dose IL-2? 

The Mirocals trial used a branded drug (Proleukin™️) that was already licensed and in use for cancer treatment. This should have meant the drug, if proven effective, would reach patients quickly, but sadly, we are faced with a continuing delay in publication of the results and lack of transparency as to the reasons for this.

We don’t have all the answers we need yet, but here we set out 3 ways to get the treatment (low dose interleukin 2) to patients and our view on what should be the priorities.

1. Off-label prescription* through NHS specials. This requires data and analysis from the trial to be available. 

This should not be the default route for most trials, but we see it as probably the fastest route to access in this particular situation. We also know that this will involve serious effort in persuading local hospital trusts and neurologists to prescribe the drug.

*Off-label is exactly what it sounds like – a prescription for conditions (or indications) that are not on the label of the drug.

This is important because any drug that is on NHS/NICE price books opens up the prospect that doctors could indeed prescribe off-label, with the support of their NHS Trust to cover the cost, IF there is sufficient scientific consensus and safety reassurance. N.B. it does not need to be authorised by NICE/MHRA for a specific condition. 

This is different to a brand-new drug candidate for MND, e.g. Tofersen. Proleukin is already approved and available via the NHS for another condition, kidney cancer. There is also good global supply and the NHS price is reasonable compared to many other drugs, at an estimated cost of around £12,000 per patient per year.

Off-label prescriptions are commonplace in oncology and many other conditions. A comparable example is Avastin, a drug approved for several forms of cancer but for over a decade almost ‘freely’ prescribed by doctors all over the UK for macular degeneration despite NOT being approved by NICE/MHRA for that condition.

Vitally, there is solid trial-based evidence for Avastin, but no application has ever been made to regulators. In a similar way to Proleukin with MND, the dose needed for Avastin for macular degeneration is much lower than for cancer, and it is just as easily re-compounded.  

2. An application by the company owning the rights to the trial drug, Proleukin, for regulatory approval. This is likely to be quicker as they already have a licence and may be able to apply for a licence variation.

It remains to be seen if this could be an option for rapid access, but we certainly believe it is a more likely faster route than 3 below.

3.  An application by another company, not involved with the trial, to develop a slightly different product/form.

This will almost certainly require a longer regulatory approval process and a new trial. N.B. This would likely take at least 5 years before authorisation.

This is the option chosen by the Mirocals Consortium together with its chosen commercial partner, ILTOO, i.e. to drive a wholly new form of the drug (a bio-similar*), known as ILT-101. The Consortium granted an exclusive licence to ILTOO to the trial data in May 2023, almost a year after the end of the trial, and ILTOO made the following statement on their website.

*we documented the challenges regarding bio-similars in our Feb 2024 Mirocals update.

We are unsure what benefits the Consortium believe outweigh the additional time in getting this treatment to patients, although we believe it involves an easier administration in future.

No doctor could/would ever prescribe a drug that has not been evaluated at all by NICE/NHS. It would be totally unethical. They certainly would not consider a drug that is not on NHS price books, let alone not manufactured on a commercial basis which is the situation with ILT-101.

We believe the Consortium is not taking the needs of patients into account in choosing the third option. They have offered no evidence to the contrary apart from some benefits with respect to storage and administration that would likely be achievable in due course anyway.

In our opinion, the focus on the regulatory package pathway is considerably delaying potential access when it should be concentrating on releasing a peer reviewed paper (even pre-print for the scientific community) of the results using Proleukin. This would potentially open the door to prescription via NHS Specials in fairly short order. 

We are now asking for an immediate realignment so that the focus is on producing the technical paper and the fastest pathways to access. This includes looking at terminating the current contract with ILTOO, which we have asked the Consortium to consider. In particular, we are asking the MND Association, a member of the Consortium, with a duty to look after patient interests, to influence such change.

In this way, neuroscientists and, most importantly, MND clinicians could come to a consensus to facilitate off-label prescription of the actual drug used in the trial BEFORE approval of the new ILTOO product that is more than likely to take several years.

We are sure you will agree that speed of access (following successful results) is more important to us than a slightly more manageable product as claimed by ILTOO. We are making this clear to all the members of the Consortium.

We must emphasise that we do not underestimate the barriers to making the drug available in the UK and anticipate the need to make our voices heard to NHS Trusts on the hoped-for publication of positive results. However, a new approach would break the current stalemate and allow us to get on with the next fight.