Getting research and treatments to adults

CEO, DMD Pathfinders 

Last Friday DMD Pathfinders co-hosted a workshop with Duchenne UK dedicated to research for adults. Specifically, in the context of a rapidly developing research pipeline of new treatments for DMD, we were asking: how can we ensure these treatments benefit adults?

The meeting was held at the International Centre for Life in Newcastle and saw clinicians, patient advocates and pharmaceutical industry reps come together to identify and address the issues involved. It was an incredibly productive meeting in terms of putting the issue very firmly on the agenda and generating significant momentum in our campaign to ensure adults are not left out with the development of new treatments.

The last meeting we attended in Newcastle, two years ago, saw the coming together of patient groups to address concerns over the fact that clinical trials were being turned down by clinics due to lack of capacity. This led to the development of the Duchenne hub, spearheaded by Duchenne UK which saw massive investment in capacity to run paediatric trials.

It was at this meeting that DMD Pathfinders, still a fledgling organisation at that stage, became aware that none of the trials on the horizon were open to adults. Not only this, no one was really asking the question about how adults would ever access potential treatments. As a result we started an adult research campaign, an idea we pitched to Duchenne UK who agreed to fund it.

Over the course of our campaign we have learned many things about the potential of developing treatment for adults with DMD.

  • We learned that since standards of care and access to specialist hospital services are so patchy, there is very little useful data about the general progression of Duchenne in adulthood. This natural history data is invaluable in assessing the effectiveness of new treatments and in improving care. During the last two years we have worked with MDUK on their Adult North Star project which they have funded to improve the data clinics collect and the standards of care provided. This is key in facilitating adult trials.
  • We learned that there is still limited understanding of what adults might expect in terms of outcomes from future treatments. There is a general consensus that once muscle has become fibrotic, it cannot be repaired, indicating that treatments can only slow down or halt progression, but cannot regenerate muscle. However there is less understanding in other areas, for example in terms of progression of DMD in the heart and to what extent that may be reversible.
  • We have closely followed the progress of various treatments at different levels of the approval process, such as Translarna (ataluren), Exondys 51 (eteplirsen) and Raxone (idebenone). We have seen various limitations placed on who is eligible for treatment, either by the regulator themselves or subsequently by the organisations that pay for treatments (insurance companies or in the UK, the NHS). This is typically based on who has been included in clinical trials, which in some cases exclude adults.
  • We identified over 40 different research companies with candidate drugs that were planning trials in DMD at some point in the future, and looked at the population that have been identified for future clinical trials. The vast majority aimed to test treatments on under 18s. This means that presently, most treatments have no plan for how evidence will be gathered and treatments made available to adults.
  • We also conducted a survey which revealed what adults think about DMD research. 61% don’t feel that research addresses the needs of adults, and a further 28% are unsure. 62% of adults are interested in trials, but there is very low confidence among people that they will actually be able to benefit from treatments in their lifetime. While most hope for the best, only 39% think it’s likely they will be able to benefit from treatments that slow down progression of Duchenne.

At the meeting on Friday we heard very clearly the message from industry that although they would like to treat adults, the primary focus is on getting a treatment approved. Based on their understanding of what regulators are looking for and the extensive scientific advice they have taken, they consider it more likely that they will be able to demonstrate that their treatment is effective by testing on a restrictive group, namely children. Since there can be big differences in how people are affected by DMD, including everyone in a trial makes it difficult to understand what difference a drug makes. In a varied group, how do you know what change is because of the drug, and what is because of natural variation? Testing on a large group of  children and adults, it is argued, makes it harder to get good evidence needed to approved treatments.

Unfortunately, gathering no evidence on adults at all, means that no one really knows if a treatment works on adults. Organisations paying for the treatments don’t want to pay for something that doesn’t work, and without evidence they feel justified in refusing to pay. We know well that it’s hard enough getting them to pay when we know that something works! If we continue to gather no evidence on adults, this will mean adults cannot access treatments when they are approved.

On the positive side, we heard about developments in care and measurement of adults with DMD. We know that we have the tools we need to run trials in adults and understand whether treatments make a difference. We have outcome measures which can reliably show how strong adults are and can be used to test treatments. This suggests if the will is there, we can run trials.

The best part of this meeting was that clinicians, charities and industry groups are now talking about how to get treatments to adults. Yes, there are complicated challenges to overcome, but there is a shared interest in working together to beat them.

There is a tremendous amount of work to do. We need to improve natural history data for adults. We need to ensure we have the best outcome measures that can be used to measure the progression of DMD throughout someone’s life. We need to ensure that the regulators do not create barriers that make it difficult to gather evidence on adults, and that they are communicating fully with industry about how evidence can be collected and used when developing treatments. We need to make sure the industry recognise the needs of adults and realise that doing nothing to understand how their treatments work on adults will hurt the industry in the long run. And we need to think creatively about how to include adults in trials, and explore other ways of gathering evidence after treatments have been approved, to ensure that adults can get the treatments in future.

DMD Pathfinders is delighted that we have been able to get this issue onto the agenda and that finally people are talking about treatments for adults. However, it’s a hollow victory if all we have achieved is an interesting conversation. We are determined to build on this success and maintain the momentum to ensure that everyone with DMD, regardless of age, can benefit from treatments to reduce the impacts of the condition.