BACKGROUND
Epidermolysis bullosa (EB) is a rare, inherited skin fragility disorder caused by mutations in genes encoding anchoring proteins of the dermal-epidermal junction. Severe forms of EB, such as dystrophic EB (DEB) and junctional EB (JEB), usually present at birth and are therefore often diagnosed soon after birth, or in early childhood. EB manifests with recurrent partial-thickness wounds and blisters which can occur anywhere on the body. A chronic cycle of wound formation, healing, and breaking down again means patients suffer with a debilitating, high wound burden, compounded by underlying genetic defects, poor nutritional status, anaemia, pain and itching.
There is currently no cure for EB, and to date no recommended treatment. Established clinical management of this lifelong disease focuses on burdensome wound management, reducing the risk of new injury, minimising complications, and improving quality of life.
In 2019, Amryt Pharma commissioned the team at Tolley to work with them as they prepared for UK market access and the launch of the first therapy for EB, Filsuvez® (birch bark extract). Filsuvez®, a topical thixotropic gel, has been shown to accelerate wound-healing during the phase III EASE trial, the largest interventional trial in EB, to date. It is indicated for the treatment of partial thickness wounds associated with DEB and JEB, in patients aged 6 months and older. The challenges encountered along the path to gaining reimbursement, and the working solutions applied, are summarised below.
CHALLENGES
Working in a rare disease area with no HTA precedence presented several challenges:
- EB was unfamiliar to several stakeholders and decision-makers ahead of the appraisal
- Clinician and patient organisations did not have direct experience with market access and HTA processes
- No previous economic evaluations/ cost effectiveness analyses had been undertaken
- As a rare disease, numbers of patients and clinical experts are relatively small, with patients treated across only four specialist centres (two adult, two paediatric)
- EB is a complex and highly heterogeneous disease, presenting challenges around the interpretation of clinical endpoints and long-term evidence from pivotal trial data
- Published evidence around natural history, resource use and quality of life is limited and mainly aggregate and/or qualitative
WORKING SOLUTIONS
- Maximising engagement opportunities with stakeholders throughout the project. An ethos of collaborative, positive working relationships with assessment bodies is crucial, in rare diseases especially, to finding agreeable solutions to a complex set of issues driven by data limitations
- Frequent and in-depth engagement with UK EB clinical experts in UK and patient organisations
- Early modelling and evidence reviews to identify key data uncertainties and develop timely solutions that included:
- Structured expert elicitation exercises
- Time-trade off exercise
- Broadened systematic reviews
- Cross-sectional study
- Steering group to coordinate simultaneous work streams across agencies
- Carer quality of life survey
Thanks to the collaborative efforts of all stakeholders, NICE recommended Filsuvez® as part of the HST programme after a single Evaluation Committee Meeting. Not only does the positive NICE recommendation change the treatment paradigm for current patients in England and Wales living with DEB and JEB, but it also paves the way for pipeline products navigating the UK HTA landscape, offering patients and their families hope for the future, as cell and gene therapies continue development.
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