Nina Buchan summarises highlights from the Westminster Health Forum conference on the future of advanced therapies in the UK
The Westminster Health Forum policy conference, Next steps for advanced therapies in the UK—research, innovation, and regulation, was held online on 9 September 2020.
Matthew Durdy, Chief Executive Officer, The Cell and Gene Therapy Catapult, opened the conference by explaining the role of The Cell and Gene Therapy Catapult in bridging the gap between academic research and industry.
Rather than providing a ‘cure’ for a disease, cell and gene therapies tackle its underlying cause to modify its symptoms. Cell and gene therapies carry a high cost up front, which can be a barrier to their uptake—especially if there are insufficient data on their use, as is often the case with rare diseases that affect a small population of individuals. However, the benefits of cell and gene therapies are realised over the lifetime of the patient. Rather than enduring repeated trials of low-cost drugs, patients may experience symptomatic relief after a single treatment. Cell and gene therapies have the potential to reduce both the burden on the health service and the need for patients to attend hospital, which is particularly relevant in the context of the COVID-19 pandemic.
At present, nine advanced therapy medicinal products (ATMPs) are licensed for use in the European Union (EU; see Table 1), but there is enormous growth in clinical trials in this area: currently, 12% of clinical trial activity worldwide is related to advanced therapeutics.1 This represents promise for a wide range of patients, but realisation of this promise is challenging when decisions on uptake are made from a 1-year cycle perspective rather than on the potential of ATMPs to free up resources and capacity over the long term.
Mr Durdy asserted that expansion of the development of ATMPs in the UK will benefit not only patients but also the economy, securing the UK’s position in the global industry, creating jobs, and attracting further businesses and investment. However, scaling up the manufacture of ATMPs for clinical trials has necessitated the creation of new manufacturing facilities. The Cell and Gene Therapy Catapult Manufacturing Centre opened in April 2018 and employs state-of-the-art infrastructure and expertise in collaboration with industry to commercialise innovations. Subsequently, the Advanced Therapies Treatment Centre (ATTC) network, a collaboration between 64 delivery partners across the NHS, industry, and academia, was established to reduce the cost of and standardise protocols for the creation of ATMPs.11 The ATTC network now runs 6% of global ATMP trials.11
Regarding the impact of COVID-19 on the cell and gene therapy sector, Mr Durdy said that the pandemic had decreased clinical trial activity, reduced manufacturing capabilities, prevented access to funding, and increased the caution exercised by industry. In addition, travel restrictions imposed during the pandemic had made the world smaller, impacting shipping. However, Mr Durdy believed that the sector does have a role in the response to the pandemic: firstly, by developing ATMPs to treat the virus, and secondly through the use of ATMPs for other indications, which will reduce the burden on the health service.
Going forward, Mr Durdy said that the cell and gene therapy sector must continue to develop high-impact therapeutics, generate data on their uses and benefits, and increase the scale but reduce the cost of manufacture. The sector must encourage the healthcare system to ‘adapt to adopt’ and break free of the short-term return paradigm. The Government must continue to invest in the sector, both in research to secure the ATMP pipeline, but also in industry to make the UK a world leader in ATMP manufacture.
A panel session followed on key issues for research and development—investment, infrastructure, workforce, and manufacturing.
Professor Uta Griesenbach, President of the British Society for Gene and Cell Therapy and Professor of Molecular Medicine, National Heart and Lung Institute, Imperial College London, stated that a worldwide skill shortage in this sector will act as a bottleneck to the growth of the industry. Professor Griesenbach asserted that a co-ordinated, UK-wide approach is required to tackle this skill shortage, and that the training provided should be standardised and of a high quality. Because advanced therapies often require special handling and storage, all those involved in prescribing and administering these therapies within the NHS should receive the training. Currently, although nine ATMPs are licensed for use in the EU, they are only used in a few, research-active hospitals, and educational materials on their use vary considerably. Professor Griesenbach said that the delivery of rigorously reviewed, high-quality training materials is planned in several waves in 2020/21. A modular format, delivered via a free e-learning platform, has been chosen to fit in with busy staff schedules, and the modules will be compatible with CPD requirements.
Next, Dr Stephen Oakeshott, Head of Innovative Technologies, Medical Research Council (MRC), described how the MRC supports the cell and gene therapy sector. Firstly, the MRC invests 70% of its budget in the research pipeline, funding fundamental research into the mechanisms underlying advanced therapeutics. Secondly, the MRC offers translational support to ensure that innovations developed in academia have a path to patients. Finally, the MRC addresses barriers to the development and manufacture of advanced therapeutics by funding infrastructure. One example is the MRC Nucleic Acid Therapy Accelerator,12 which is underpinned by collaboration between the academic, industrial, and charity sectors in state-of-the-art facilities, and aims to accelerate the development of nucleic acid therapies.
Concluding this session of shorter presentations, Dr Keith Foster, Chief Scientific Officer, Sutura Therapeutics, explained why the definition of an ATMP must be updated. At present, the following are classed as ATMPs:13
- somatic cell therapy medicinal products, which contain cells or tissues that have been manipulated to change their biological characteristics, or cells or tissues not intended to be used for the same essential functions of the body
- gene therapy medicinal products, which work by inserting genes into the body
- tissue engineered products, which contain cells or tissues that have been modified in order to repair, regenerate, or replace a tissue or organ
- combined ATMPs, which contain one or more medical devices as an integral part of the medicine, such as cells embedded in a biodegradable matrix or scaffold.
Synthetic genes are not legally classified as ATMPs, but many medications based on synthetic genes are currently in clinical trials. Dr Foster argued that redefining ATMPs to include synthetic genes represents an important opportunity: altering the legal status of these innovations will achieve a better regulatory framework, a smoother approval process, increased certainty, and accelerated reimbursement, and may incentivise new biotechnology firms to develop synthetic gene products. However, capacity is currently poor, there is no standardised ethical review process, and clear manufacturing policies are lacking for the production of synthetic gene products. Engagement with industry will be necessary to bring about change, but this may prove challenging, as many manufacturers favour ‘big ticket’ treatments over therapies for rare diseases. Dr Foster concluded by saying that policy driven changes are needed to incentivise research to address areas of unmet need—but also that ‘no access to approved medications is worse than no drug’.
Dr Nick Crabb, Programme Director, Scientific Affairs, NICE, spoke about the assessment and approval of advanced therapies. Dr Crabb asserted that NICE appraisal frameworks are applicable to advanced therapies, but that there are issues around the clinical uncertainties associated with these medicines. A combination of high cost and high clinical uncertainty means that innovative payment methods are often necessary.
Discount schemes have already had a big impact on the appraisal process for advanced therapies. To date, NICE has issued guidance on 10 products and/or indications. In nine cases, the recommendation was positive, but this was often dependent on a managed access arrangement to mitigate risk related to clinical uncertainty. Dr Crabb cited the example of the first-in-class CAR-T medication tisagenlecleucel, which is indicated for the treatment of B-cell acute lymphoblastic leukaemia in patients aged up to 25 years.5 Tisagenlecleucel was assessed through the NICE Technology Appraisal system, for which the incremental cost-effectiveness ratio cap is £20,000–30,000 per quality-adjusted life year. At £282,000 per infusion, tisagenlecleucel far exceeded this threshold, so could not be recommended for routine commissioning. However, after negotiating a commercial-in-confidence discount with the manufacturer, NICE was able to recommend tisagenlecleucel for use through the Cancer Drugs Fund (CDF).
A few years ago, with no managed access schemes or CDF, the decision for tisagenlecleucel would have been negative. Instead, its use through the CDF will allow patients access to the medicine and enable further data collection to determine the drug’s clinical and cost-effectiveness. In future, the CDF may be extended to form an ‘Innovative Drugs Fund’, facilitating similar managed access to innovative medicines outside the sphere of cancer treatments.
Jeremy Taylor, Director for Public Voice and Director of the Centre for Engagement and Dissemination, National Institute for Health Research (NIHR), explained the role of the NIHR as a key research partner of the NHS. The NIHR provides funding, support, and infrastructure to enable the translation of research into practice.
Mr Taylor stated that focussing on the scientific and economic aspects of advanced therapies can risk overlooking the perspectives of patients and the public. Determining unmet need and designing and conducting clinical trials are reliant on patients, but participants are often not informed of the outcomes of clinical trials. Although further investigation is needed, patients in need of advanced therapeutics may require a special approach for inclusion in clinical trials—patients with a rare disease and limited treatment options may be physically or psychologically vulnerable, and may be more willing to accept a greater risk or burden of treatment than other patients.
The effects of clinical trials on individuals with rare diseases is an issue with the potential to affect the future and growth of the advanced therapeutics sector; to address this, the NIHR ATMP Co-ordinating Group, a working group chaired by Jayne Spink, Chief Executive Officer of Genetic Alliance UK, will examine patient and public involvement to determine whether a specific approach to clinical trials is necessary in patients with rare diseases.
This conference report was prepared by Specialised Medicine and the speakers have not had the opportunity to make corrections.
- Catapult Cell and Gene Therapy. The Cell and Gene Therapy Catapult UK clinical trials database. catapult.org.uk/clinical-trials-database (accessed 6 October 2020).
- NICE. Betibeglogene autotemcel for treating transfusion-dependent beta-thalassaemia ID968. Guideline in Development [GID-TA10334]. www.nice.org.uk/guidance/indevelopment/gid-ta10334 (accessed 6 October 2020).
- NICE. Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations. Highly Specialised Technologies Guidance 11. NICE, 2019. Available at: www.nice.org.uk/hst11
- NICE. Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after 2 or more systemic therapies. Technology Appraisal Guidance 559. NICE, 2019. Available at: www.nice.org.uk/ta559
- NICE. Tisagenlecleucel for treating relapsed or refractory diffuse large B-cell lymphoma after 2 or more systemic therapies. Technology Appraisal Guidance 567. NICE, 2019. Available at: www.nice.org.uk/ta567
- NICE. Darvadstrocel for treating complex perianal fistulas in Crohn’s disease. Technology Appraisal Guidance 556. NICE, 2019. Available at: www.nice.org.uk/ta556
- NICE. Autologous chondrocyte implantation using chondrosphere for treating symptomatic articular cartilage defects of the knee. Technology Appraisal Guidance 508. NICE, 2018. Available at: www.nice.org.uk/ta508
- NICE. Strimvelis for treating adenosine deaminase deficiency–severe combined immunodeficiency. Highly Specialised Technologies Guidance 7. NICE, 2018. Available at: www.nice.org.uk/hst7
- NICE. Talimogene laherparepvec for treating unresectable metastatic melanoma. Technology Appraisal Guidance 410. NICE, 2016. Available at: www.nice.org.uk/ta410
- NICE. Holoclar for treating limbal stem cell deficiency after eye burns. Technology Appraisal Guidance 467. NICE, 2017. Available at: www.nice.org.uk/ta467
- Catapult Cell and Gene Therapy. Press release: Annual Review 2020 highlights impact on growth and productivity in the UK cell and gene therapy industry. catapult.org.uk/news-media/general-news/press-release-annual-review-2020-highlights-impact-growth-and-productivity-0 (accessed 6 October 2020).
- UK Research and Innovation. Introducing NATA; the Nucleic Acid Therapy Accelerator. ukri.org/news/blog/introducing-nata/ (accessed 6 October 2020).
- Parliamentary Office of Science & Technology. Regulating advanced therapies. London: Parliamentary Office of Science & Technology, 2017. Available at: post.parliament.uk/research-briefings/post-pn-0567/