ISPOR Europe Round-up: “Gene Therapies: Where High Promise Meets High Uncertainty, How Should HTA Methodologies Appropriately Value and Enable Access?”

In November, ISPOR Europe was hosted in person for the first time since 2019 at the Austria Centre, Vienna. In front of a full theatre, OHE’s Professor Adrian Towse introduced the session and speakers:

• Dr Amanda Cole, Senior Principal Economist at OHE
• Josie Godfrey, Director at JG Zebra Consulting
• Dr Ruth Kim, Value & Evidence Team Leader, Rare Disease and Internal Medicine at Pfizer
• Dr Oriol Sola-Morales, Chair & Founder of the HiTT Foundation

The first speaker, Amanda, provided an overview of our recent report that addressed the titular question and discussed actionable recommendations resulting from an expert roundtable. The report identified four broad categories of challenges faced by gene therapies undergoing health technology assessment (HTA): initial assessment of clinical effectiveness, assessment of costs, uncertainty regarding long-term outcomes and incorporating additional value elements. The actionable recommendations focused on better capturing the value of gene therapies and addressing uncertainty in outcomes during HTA.

Next up, Josie presented her insights from a patient advocacy perspective. She discussed Project Hercules, a multinational collaboration set up by Duchenne UK, as an example of how patients’ voices can be heard in the context of gene therapies. This initiative uses a patient-centred approach, with input from clinicians, academics, leading pharmaceutical companies, HTA agencies and other advisers to build a better evidence base for Duchenne Muscular Dystrophy (DMD). Project Hercules also developed a bespoke quality of life measure (DMD-QoL) which incorporates aspects of quality of life that are important to DMD patients and their families; Josie also called for more research into quality of life measures for carers.

Presenting the industry perspective, Ruth explained that in the context of gene therapies, the appropriate primary endpoints for clinical trials are still being considered. Hence, the discussion of appropriate surrogate endpoints is in its infancy. She called for patients to lead and guide these discussions, given that they can accurately describe their treatment pathway and the healthcare system. Ruth suggested that our thinking should shift to outcomes or other value-based agreements to take pressure away from payers and allow for risks and benefits to be shared. For these novel agreements to be executed, relevant patient outcomes for collection should be agreed upon, building on learnings from the oncology space.

Finally, Oriol addressed the “elephant in the room”: affordability from the payer perspective. He proposed moving away from the Fee for Services (FFS) model to a producer of services paradigm to address equity concerns. Oriol also questioned whether the relatively high prices of gene therapies would remain the same in the long run. He suggested that – to serve patients better – we should orient the development of new therapies to ensure they target the needs of patients.

To wrap up the symposium, Adrian moderated a Q&A session, taking questions from the in-person and online audience. One audience member asked about the importance of involving HTA bodies at an early stage. Josie suggested that the panel and audience would agree that the earlier you recognise any potential evidence generation challenges and begin the conversation between HTA, manufacturers, patients and payers, the sooner you can begin to resolve the issue. Indeed, one of the recommendations proposed in OHE’s report is to enable early stakeholder dialogue to align on feasible and appropriate HTA evidence packages. Another audience member questioned the feasibility of gene therapies being found cost-effective if the comparator is a relatively cheap standard of care. Ruth argued that we should first consider whether there is an unmet need before considering the current standard of care. She proposed that patients’ insights into their treatment pathways should inform cost-effectiveness analysis and that appropriate patient-reported outcome measures (PROMs) should be used to capture quality of life. Amanda added that as a society, we care about addressing unmet needs and treating severe diseases; this is why alternative HTA criteria for treatments for very rare diseases have been applied through special evaluation routes, such as NICE’s Highly Specialised Technology pathway – whether those criteria are appropriate and/or sufficient is a matter of much debate. There were many more thought-provoking questions, and a lively discussion among the panel before Adrian ended the session.

For more insights into the challenges of appropriately assessing gene therapies, an example case study examining HTA decisions across a selection of European countries and a detailed discussion of our actionable recommendations, read our full report here.