A review of the challenges and proposals for improving patient access to advanced therapeutic medicinal products in England

Executive Summary

RARE IMPACT is a multi-stakeholder initiative working to improve patient access to advanced therapy medicinal products (ATMPs). This patient-focused initiative aims to assess challenges and propose actionable solutions to concerns regarding access to these transformative rare disease treatments in Europe. Through engagement with health technology assessment (HTA) agencies, regulatory bodies, payers, patient groups, clinicians, manufacturers and other experts across Europe, RARE IMPACT partners identified challenges and have proposed solutions for better access to ATMPs in Europe.

This report aims to stimulate multi-level stakeholder discussions on patient access to ATMPs and is not intended to capture all challenges to patient access to ATMPs. The RARE IMPACT initiative was launched at the European Conference on Rare Diseases and Orphan Products in 2018.

To date, patient access to ATMPs in England has been relatively good, with largely positive decisions from the National Institute for Health and Care Excellence (NICE) on both gene and cell therapies appraised in the last 18 months

This may reflect a particularly supportive political environment for ATMPs currently. Despite these positive precedents, there are systemic challenges that bring into question the sustainability of access to ATMPs in the UK (particularly if political enthusiasm wanes). The Medicines and Medical Devices Bill was reintroduced in the Queens Speech in December 2019, putting it on the agenda for the current government. The bill is part of a strategy to promote growth in the life sciences sector and will look to remove barriers to access to innovative therapies.

The primary challenges relate to HTA assessment methods, the willingness to pay for innovation (especially in small populations), and accessibility challenges where clinical services are not currently aligned with ATMP requirements

Assessment challenges for ATMPs reflect a misalignment between HTA methodology and evidence generation for potentially curative treatments in small populations. For example, while NICE allows the extrapolation of short-term data to long-term outcomes, this is very difficult in practice, particularly for diseases in which there is an absence of natural history data. Similarly, where the comparator in the pivotal trial is not the standard of care (SoC) in England, NICE will allow indirect comparisons, yet in the absence of common control arms this may not be possible. This challenge was observed in the NICE appraisal of Kymriah in relapsed/remitting diffuse large B-cell lymphoma (R/R DLBCL). NICE is currently revisiting its HTA methods, which represents an opportunity to refine approaches to the assessment of ATMPs. Consideration should be given to providing guidance on a standardised approach to extrapolating short-term data, incorporation of data from single-arm trials and methods for indirect treatment comparisons (ITC) for ATMPs.
More clarity should be given on the evidence that is required to address data uncertainty within patient access schemes and managed access agreements for ATMPs.

Adaptive assessment processes can also reduce evidential uncertainty. While NICE and NHSE have multiple mechanisms that allow for evidence generation and adaptive assessment, there is currently no appropriate routine option for ATMPs. Existing approaches, particularly managed access agreements and Cancer Drug Fund mechanisms, should be further developed to allow ATMPs to be routinely assessed through adaptive processes that reflect the value of the innovation while reducing the clinical uncertainty for the NHS.

A related challenge concerns the multiplicity of reimbursement pathways for orphan ATMPs in England and Wales. These include NICE Single Technology Appraisal (STA), NICE Cancer Drug Fund (CDF), NICE Highly Specialised Technology (HST) Programme, the Clinical Priorities Advisory Group and direct commissioning from NHSE. Incremental cost-effectiveness ratio (ICER) thresholds vary according to pathway, from £20K to £300K per quality-adjusted life year (QALY). There is considerable uncertainty about the route through which any particular ATMP is likely to be assessed. A single sustainable pathway for the assessment of ATMPs for rare diseases in England and Wales would provide greater certainty and allow for more tailored assessment methods.

Affordability (willingness to pay) is potentially a major impediment to future orphan ATMP access in England and Wales, as it has been for orphan drugs in general. Flexible commercial arrangements have been identified as a potential solution. NHSE is currently seeking consultation on a proposed Commercial Framework that provides more guidance on how it intends to negotiate commercial agreements in future. It is important that this framework is appropriate for ATMPs. In particular, it should create the option for staggered (annuity) payments, ensure sufficient flexibility in deal structures to reflect the specificities of individual ATMPs, and simplify and expedite the process of negotiating commercial agreements. Given the particular challenges associated with ATMPs, it will also be important to further build ATMP expertise and infrastructure within the NHS commissioning process, to allow for better informed discussion on payment models.

Accessibility is also a major consideration as the delivery of ATMPs is complicated due to their personalised nature. Accessibility challenges exist in the NHS in situations where clinical services are not currently aligned with ATMP requirements. Although NHSE has moved quickly to adapt processes where needed, change to service provision inevitably takes time and represents a barrier to adoption. A systematic analysis of the number of future ATMPs, the typical support services required, and the geographic dispersion is necessary to inform health service planning. At the individual ATMP level, considerations of the health service impact of a new treatment should be addressed as early as possible through horizon scanning to better prepare providers and reduce the time to patient access.

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