In recent years, the emergence of Advanced Therapy Medicinal Products (ATMPs) has revolutionized the landscape of medical treatment, offering groundbreaking options for diseases that were previously untreatable. These therapies, which include gene therapies, cell therapies, and tissue-engineered products, hold the promise of significant clinical benefits and potentially curative outcomes. However, their evaluation and integration into healthcare systems pose unique challenges. This blog delves into the evaluation of ATMPs by the National Institute for Health and Care Excellence (NICE) in the UK, highlighting the methodologies, challenges, and future directions.
Understanding ATMPs
ATMPs are classified into three main categories:
1. Gene Therapy Medicinal Products: These involve the transfer of genetic material into cells to treat or prevent disease.
2. Somatic-Cell Therapy Medicinal Products: These include cells that have been manipulated to alter their biological characteristics to treat disease.
3. Tissue-Engineered Products: These involve cells or tissues that have been modified to repair, regenerate, or replace human tissue.
Given their complexity, the evaluation of ATMPs requires a nuanced approach that considers not only their clinical effectiveness but also their long-term impact, safety, and cost-effectiveness.
NICE’s Role in Evaluating ATMPs
NICE is a key organization in the UK responsible for assessing the value of medical treatments and technologies. Its evaluation process for ATMPs involves several steps, including evidence review, economic evaluation, and consultation with experts and stakeholders.
Evidence Review
NICE evaluates clinical evidence from various sources, including randomized controlled trials (RCTs), observational studies, and expert testimonies. However, the limited availability of long-term data for many ATMPs poses a significant challenge. For instance, therapies like axicabtagene ciloleucel and tisagenlecleucel have shown promising results in treating certain cancers, but their long-term effectiveness and safety remain uncertain.
Table 1: Examples of ATMPs Evaluated by NICE
| Therapy | Condition Treated | Initial Approval Year | Key Challenges |
| Axicabtagene ciloleucel | Diffuse large B-cell lymphoma | 2018 | Long-term effectiveness |
| Tisagenlecleucel | B-cell acute lymphoblastic leukemia | 2018 | High cost, generalisability |
| Voretigene neparvovec | Inherited retinal dystrophies | 2019 | Long-term impact, cost |
| Onasemnogene abeparvovec | Spinal muscular atrophy | 2020 | Financial risk, safety |
Economic Evaluation
Economic evaluation is a critical component of NICE’s assessment. It involves analyzing the cost-effectiveness of ATMPs using metrics like the Quality-Adjusted Life Year (QALY). The high upfront costs of ATMPs, coupled with uncertainties about their long-term benefits, complicate this process. For example, the one-time treatment costs of gene therapies such as voretigene neparvovec and onasemnogene abeparvovec are substantial, and their cost-effectiveness must be assessed over a patient’s lifetime.
Table 2: Cost-Effectiveness of Selected ATMPs
| Therapy | Estimated Cost | QALY Gained | Cost per QALY |
| Axicabtagene ciloleucel | £300,000 | 2.5 | £120,000 |
| Tisagenlecleucel | £280,000 | 3.0 | £93,333 |
| Voretigene neparvovec | £600,000 | 4.0 | £150,000 |
| Onasemnogene abeparvovec | £1,600,000 | 10.0 | £160,000 |
Challenges in Evaluating ATMPs
Generalisability of Research
One of the primary concerns with ATMPs is the generalisability of research findings. Clinical trials for these therapies often involve small, specific patient populations, which may not reflect the broader population that will receive the treatment. This issue is exemplified by therapies like tisagenlecleucel and darvadstrocel, where patient characteristics in trials did not always match those of typical NHS patients.
Financial Risks
ATMPs pose significant financial risks due to their high costs and the potential for irrecoverable expenses if the therapies do not provide long-term benefits. This financial uncertainty is particularly challenging for health systems with fixed budgets, such as the NHS. NICE has explored outcome-based contracts and other risk-sharing agreements with pharmaceutical companies to mitigate these risks.
Wider Societal Impacts
ATMPs can have broader societal impacts, including effects on patients’ families and caregivers. These impacts can be both positive (e.g., reduced caregiving burden) and negative (e.g., increased need for long-term care for patients with extended life expectancy but significant disabilities). However, quantifying these impacts and incorporating them into cost-effectiveness analyses is complex and often overlooked.
Future Directions
To address these challenges, NICE has considered several adaptations to its evaluation process:
1. Flexible Non-Reference Case Analysis: Allowing more flexibility in evaluating the unique aspects of ATMPs, such as accepting higher uncertainty in certain cases.
2. Integration of Qualitative Evidence: Incorporating qualitative data on patient and caregiver experiences to provide a more comprehensive assessment.
3. Special Funding Arrangements: Exploring innovative funding models, including risk-sharing agreements and outcome-based payments, to manage financial risks effectively.
Conclusion
The evaluation of ATMPs by NICE highlights the complexities and challenges associated with these advanced therapies. While ATMPs offer significant potential benefits, their high costs, limited long-term data, and broader societal impacts require a sophisticated and flexible approach to assessment. By adapting its methodologies and exploring new funding models, NICE aims to ensure that patients can access these groundbreaking treatments while maintaining the sustainability of the healthcare system.
References
1. National Institute for Health and Care Excellence. “Our principles.” London.
2. National Institute for Health and Care Excellence. “Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years.” [NICE Guidance](https://www.nice.org.uk/guidance/ta554/history).
3. National Institute for Health and Care Excellence. “Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after 2 or more systemic therapies.” [NICE Guidance](https://www.nice.org.uk/guidance/ta559/history).
4. National Institute for Health and Care Excellence. “Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations.” [NICE Guidance](https://www.nice.org.uk/guidance/hst11/history).
5. National Institute for Health and Care Excellence. “Onasemnogene abeparvovec for treating spinal muscular atrophy.” [NICE]