Research and licensing medicines: the funder’s perspective
While I’m pleased to be contributing to the Empower blog, it’s also a cause of deep sadness to be writing here so soon after the passing of Les Halpin, an inspirational man whose passion and enthusiasm for his cause I greatly admired. I’m glad to hear that his work will be continued by the Empower campaign.
I wanted, however, to give a perspective on this important debate from the point of view of a funder of research. Funding and supporting research into MND is one of the core elements of the MND Association’s mission. We put over £2.5million into MND research each year, and have a portfolio of projects costing over £8million. The distance to travel before we find a cure remains great, but there is good reason to be excited about the journey: there are many recent breakthroughs to build on, and the basic approach to how we conduct research could be on the verge of significant change.
The Empower campaign has rather captured the zeitgeist of the debate around research methodologies and regulation. At EU level, the heavy-handed Clinical Trials Directive is being replaced with a more proportionate regulation, while at home the MHRA has proposed an early access scheme for new medicines, NHS England is introducing its Commissioning through Evaluation scheme, and NICE has started evaluating medicines for off-label use (though unfortunately none of these routes is likely to feature an MND treatment any time soon).
But an even bigger change is in the air: technology is enabling not just the sharing of self-reporting by patients, but also the sharing by researchers of large, population-wide datasets on an international basis; this could make it possible to get new drugs to patients earlier, monitoring their effects while maintaining the rigour of traditional randomised controlled trials. Policy-makers have noticed these possibilities, and are starting to work out how such a model, so-called adaptive licensing, might function: who would monitor and analyse the incoming data, what safeguards would be needed to ensure both patient safety and that sufficient robust data is generated, and so on. The MND Association is in touch with the European Medicines Agency on the subject, and though this connection we will be presenting at an international conference organised by the Drug Information Association in Vienna next March.
That said, a model for conducting trials by getting drugs to wider populations at an earlier stage is not with us yet. The double-blinded, randomised, placebo-controlled trial remains the gold standard, and we have yet to work out how to secure a similar level of rigour, and ensure that meaningful results can be confidently demonstrated, within the inevitable statistical noise of real-world trials . But I hope that, once the necessary methodologies exist, the MND Association will be investigating how it can contribute towards such trials in the future.
No methodological advance in trial design will wipe out the considerable challenges of understanding and fighting neurodegenerative disease, however: it is not only MND and orphan diseases that have lacked major breakthroughs to slow or prevent the illness, but also common conditions, be they acute such as stroke, or chronic and progressive such as Alzheimer’s disease. Even where therapies exist, for instance for Parkinson’s disease, they address symptoms rather than slowing progression; the basic approach of even the most modern of these treatments is now forty years old. In relation to MND, over twenty-five compounds have been through phase II / phase III trials since riluzole was made available, and all have failed. This depressing statistic highlights the fact that there are more fundamental challenges to be overcome, upstream of the debate around access to medicines, in understanding disease pathogenesis and selecting the right biochemical ‘targets’ for therapeutic intervention. Moreover, even if we identify an effective new drug, the fact remains that much of the damage to motor neurones occurs before a person even starts to shows symptoms, so the potential benefit will be lessened unless we can greatly improve diagnosis.
Of course, this list of challenges, however long, is only half the picture. There are reasons for optimism: in the last two decades we have discovered many of the genetic causes of the inherited form of MND, demonstrated the benefits of non-invasive ventilation in MND and secured NICE guidance to promote its use across the NHS, and increased the use of multi-disciplinary care and interventions such as gastrostomy that have the potential to improve both longevity and quality of life.
That there is undoubtedly more such progress to come is, of course, little consolation to those living with MND today. Whenever our researchers set up clinical trials, I am always impressed by the enthusiasm of many people with MND to participate in them: these are experiments first and foremost, and the benefits of the knowledge gained from them will flow to future generations. Participants appreciate that they may well not receive any therapeutic benefit, either because they are on a placebo or because the drug has little effect (though even negative results are valuable in shaping the design of future trials). Whatever shape our research takes in the future, the selfless willingness of people with MND to take part will remain an essential part of it.