A new alliance in Duchenne muscular dystrophy aims to change the landscape of orphan drug assessment

We are all waiting for a game-changer in Duchenne muscular dystrophy (DMD). The need is obvious, and the research that is underway is incredibly exciting. But what if the most significant development in accelerating a treatment for DMD was not a medicine at all? What if the biggest innovation was collaboration?

January 2018 marked a quiet revolution in the industry’s approach towards access to medicines for rare diseases. It was announced that seven global pharmaceutical companies (Pfizer, PTC Therapeutics International, Roche, Sarepta Therapeutics, Solid Biosciences, Summit (Oxford) and Wave Life Sciences USE) would, for the first time, work together to generate, align and share disease-level data across an entire condition, as part of a pioneering initiative entitled HERCULES (Health Economics & outcomes Research Collaborative United Leading Evidence Synthesis).

Spearheaded by charity Duchenne UK, alongside two academic partners (the Universities of Leicester and Sheffield), the HERCULES collaboration will build a single evidence base for DMD, suitable for use by any health technology assessment agency anywhere in the world – whether it’s for the National Institute of Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), the Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) or the Pharmaceutical Benefits Scheme (PBS).

Looking ahead, the advantages of this approach are considerable – and could herald an era of greater clarity, certainty and even a swifter, more straightforward assessment process for medicines treating DMD. And looking even further ahead, if this approach proves successful, it could transform the way the industry looks at health technology appraisals (HTAs) for rare diseases.

The need for new approaches in rare diseases

The challenges of introducing new medicines to treat rare diseases are numerous and well-documented. Rare conditions affect around 3.5 million people in the UK and 30 million people across Europe. Yet only five percent of rare diseases have a licensed treatment option in the UK. And all too often, even when a licence is granted for a medicine in a rare disease, it can experience delays during the HTA appraisals process, which almost inevitably delays its availability to patients.

The challenges of collecting data from a comparatively small patient pool are significant, and are multiplied when a number of different companies are all conducting studies in broadly the same patient population. HERCULES will address this in DMD, and participating companies will share disease level data, potentially including from the placebo arms of their studies, to develop a consistent picture on questions such as overall disease burden and impact on quality of life.

Sharing resources on HTA submissions

Alongside creating a consistent and shared evidence base, HERCULES has other advantages for partner companies. In order for HTA bodies to recommend funding for particular medicines, companies are required to develop a comprehensive value dossier that includes data collection, economic modelling and quality of life measurements. These vital components of a submission can be difficult, time-consuming and expensive for all but the best resourced companies to generate.
HERCULES will allow partners to share many of these costs; giving smaller, entrepreneurial companies the same chances as their larger, better resourced counterparts.

Any situation in which multiple companies each submit dossiers on their intervention rapidly highlights any potential dissimilarities in the way these organisations present their evidence, with additional potential for inconsistent presentation of necessary information, which need to be resolved as part of the appraisals process.

This can greatly slow down the HTA decision-making process in rare diseases, as HTA bodies return to individual companies multiple times to have different queries answered. And it is a process that can be repeated each time a new company seeks an appraisal. No-one – least of all the patients affected – wants to see multiple iterations and appeals, with all the delays this entails. HERCULES addresses this, creating a consistent, shared approach at the outset, for the benefit of all future submissions.

How HERCULES will shoulder the weight in DMD

Phase One of HERCULES has begun and will focus on understanding the current evidence base, the cost of DMD and lives lost to it, as well as current measures of success in DMD clinical trials. To achieve this, HERCULES’ activities will include developing:

  • A critique of the existing measures of Quality of Life (due mid-2018)
  • Analyses of available data that will include mapping clinical trial endpoints to clinical outcomes, to be used in disease modelling and evidence that are meaningful for HTA and reimbursement decisions (by end 2018/early 2019)
  • A core economic model for use in the appraisal of new treatments for DMD which individual companies can adapt to their products (by Spring 2019)
  • A Burden of Illness study to provide a comprehensive measure of the impact of DMD on patients and families (Spring 2019)
  • A new Quality of Life metric that will better capture important elements of DMD (by mid-2019).
    Duchenne UK hopes, through the collaborative approach of HERCULES, to build the most robust evidence base possible in DMD. This will in turn create more certainty, as well as generating an economic model that is both robust and relevant.

A way forward for all rare diseases?

At the heart of HERCULES is the desire to improve outcomes for all involved in medicines development and approvals in DMD, especially for the children living with this condition who are waiting for potentially life-changing treatments. Around 2,500 boys are affected by DMD in the UK and around 300,000 worldwide. DMD is the most common fatal genetic disease diagnosed in childhood, almost exclusively affecting boys.

Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood, and many use a wheelchair by around the age of 12. As deterioration continues, it leads to paralysis and early death, often in their 20s. There currently is no treatment or cure, and there is therefore a critical need for new therapies.

Duchenne UK hopes that HERCULES will simplify and accelerate the appraisals of new treatments for boys with DMD. However, the true impact of HERCULES could go much further than that. If we can establish an effective, streamlined approach to HTA and reimbursement in DMD, this paves the way for the approach to act as an exemplar to be replicated in many other rare diseases.
At Duchenne UK we believe this level of collaboration is incredibly exciting, not simply because it is a first, but because it could transform the prospects for those in other rare diseases for which new options are desperately needed.