Advanced Therapy Medicinal Products (ATMPs) are leading in healthcare innovation, providing potentially curative, one-time treatments that offer long-term benefits for patients.1
The European Medicines Agency (EMA) defines ATMPs as medicines for human use that involve genes, tissues, or cells, providing innovative treatments for diseases and injuries. They are mainly classified into three categories: gene therapy medicines, somatic-cell therapy medicines, and tissue-engineered medicines. Some ATMPs also include medical devices as essential parts, known as combined ATMPs.2
ATMPs possess specific characteristics that set them apart from traditional medicines:1
- Indicated in diseases with significant unmet needs (e.g., oncology)
- Require only a single administration
- Majority of ATMPs target rare diseases
Consequently, regulatory agencies have demonstrated a willingness to accelerate the approval process for ATMPs, resulting in their consideration for expedited regulatory pathways such as Conditional Market Authorisation and PRIME (PRIority MEdicines) designation.3,4
However, the unique features of ATMPs pose specific challenges for pricing and reimbursement. The latest EMA quarterly report noted that only a limited number of ATMPs are currently reimbursed and available in Europe.5 Typically, clinical trials for ATMPs are small, involve diverse patient groups, are of short duration, and use single-arm designs. These trials are further complicated by the challenges of developing treatments for rare and ultra-rare conditions, such as the lack of natural history data, unclear endpoints, and inadequate or non-existent comparisons. As a result, the evidence provided by manufacturers is often considered insufficient by health technology assessment (HTA) bodies, causing uncertainty about the full potential of ATMPs in terms of both their impact and long-term effects. Furthermore, the one-off cost of ATMPs is considerably higher than that of continuously dosed medicines.6
Funding ATMPs is challenging because their value primarily depends on potential long-term benefits, such as cost savings. This article examines real-world case studies of successful and complex ATMP pricing in Europe, highlighting effective strategies, failures, and their underlying reasons.
Contracting approaches for ATMPs
Across Europe, payers continue to use traditional methods to control ATMP prices, including confidential rebates, price–volume limits, and patient-access schemes (such as England’s Commercial Access Agreements and Scotland’s Patient Access Schemes).7-9 These are often considered before shifting to advanced managed-entry agreements (MEAs) that link coverage to real-world evidence.
Two emerging contracting approaches have gained popularity to mitigate risks related to ATMPs:9
- Outcome-based agreements (OBAs), a type of MEA where the manufacturer’s revenue depends on how well the therapy performs post-launch
- Split-payment (annuity) models tackle the challenge of high upfront costs for ATMPS. Payments are spread over several years, with later instalments cancelled if milestones are not achieved, helping to maintain budget stability without lowering the list price
Additionally, health systems have created dedicated funding pathways to give patients early, though temporary, access to promising ATMPs while more evidence is gathered. For example, England’s Cancer Drugs Fund (CDF) now operates alongside the new, similar Innovative Medicines Fund, which provides managed access to non-cancer medicines.8,10
Collectively, these strategies offer European payers a versatile toolkit to manage affordability and uncertainty as more ATMPs become available.
Success Case Studies
Recently, several ATMP launches have adopted innovative pricing and reimbursement strategies, allowing patient access despite significant uncertainty and high costs. The examples below illustrate successful methods used across various European markets.
Table 1: Examples of successful ATMP launches in Europe
| Example | Contracting mechanism | Why did it succeed? |
|---|---|---|
| England – Kymriah (tisagenlecleucel) & Yescarta (axicabtagene ciloleucel) Chimeric antigen receptor T-cell (CAR-T) therapies List price ~ £282,000 (Kymriah) & £280,000 (Yescarta) | CDF: – Confidential discounts + compulsory RWE collection – NICE scheduled a fixed-date re-appraisal once survival and response data matured | – The CDF delivered near-immediate patient access while shielding NHS budgets until uncertainty of durability was resolved – Both products received full NICE approval after the RWE review, validating the approach |
| Italy – Zolgensma (onasemnogene abeparvovec) Spinal muscular atrophy (SMA) gene therapy List price ~ €2.15 million | “Pagamento a risultato” (pay-at-result) negotiated by AIFA: – Price divided into four equal tranches at 12, 24, 36 and 48 months – Each tranche is payable only if the child meets pre-specified survival or motor-function milestones – Additional confidential discount and a 24-month review clause | Allowed broad reimbursement (all SMA Type 1 patients < 13.5 kg) while spreading cash flow over four fiscal years and ensuring the NHS pays only for success |
| Italy & Spain – Kymriah (tisagenlecleucel) & Yescarta (axicabtagene ciloleucel) CAR-T therapies List price ~ €320,000-327,000 (Kymriah) & ~ €327,000 (Yescarta) | Registry-anchored national OBAs: 1. AIFA registries – Kymriah: payments at infusion, 6 months, 12 months if durable response – Yescarta: higher uncertainty – first payment deferred to 6 months, then 12 months contingent on response 2. VALTERMED national outcomes platform – ~50 % of list price paid upfront; remaining instalments at 6, 12 or 18 months if the patient responds | Trusted national registries automate payment triggers, shield payers from non-response costs, and enable a swift, nationwide rollout of CAR-T treatments |
Cautionary and Complex Case Studies
Not all ATMP launches have proceeded smoothly – some have encountered significant issues with pricing and access, serving as cautionary examples. Here, we examine key cases where pricing or reimbursement barriers hindered the therapy’s success.
Table 2: Examples of cautionary and complex ATMP cases in Europe
| Example | Market-access barrier | What went wrong or the key lesson learned |
|---|---|---|
| Zynteglo (betibeglogene autotemce) & Skysona (elivaldogene autotemcel) Gene therapies | Securing an acceptable price in major EU markets | – Significant price disparity: €1.57 m asking price versus approximately €0.77 m German offer – No early outcomes-based compromise proposed, leading to stalled negotiations – Payers remain unconvinced about long-term durability and considered viable alternatives (transfusion + chelation) |
| Roctavian (valoctocogene roxaparvovec) Gene therapy | Demonstrating value (e.g., clear superiority or cost-offsets) versus evolving standard treatments | – Uncertainty about the long-term benefits – Clinical trials demonstrated a significant reduction in bleeding and factor VIII usage in the first 1-2 years, but also indicated that the effect diminishes over time as factor levels – One-time €1.5 million cost compared poorly with cheaper, well-established prophylaxis (e.g., emicizumab) |
| Strimvelis (autologous CD34+ cells) Gene therapy | Sustaining access amid logistical and safety hurdles | – Manufacture/administration confined to a single Milan site—low throughput and travel burden – 2020 leukaemia case raised safety concerns, pausing use – Small patient volume received treatment, plus bespoke process, made cost recovery and multi-country rollout unviable |
References: 13-15
Conclusion
By examining successful and cautionary cases, we can gain key insights into why certain ATMP pricing strategies appeal to payers and how to improve the likelihood of achieving successful market access. Here is a summary of important considerations for future ATMP launches:
- Engage with payers 18 to 24 months before product launch to secure market access and favourable pricing by understanding and addressing their needs. This early communication enables the joint development of solutions by discussing evidence requirements, budget impacts, and engaging with regulatory and HTA bodies to align expectations and minimise the evidence gap between the product and payer needs
- Design trials and post-launch studies not only for regulatory approval but also with reimbursement considerations. Include clinically meaningful, payer-relevant endpoints and plan to collect real-world evidence to resolve uncertainties, such as establishing a long-term registry for durability
- Be innovative and adaptable when suggesting financing models; this could be the key to turning a payer’s response from “too expensive” to “we can handle this if it is structured differently”
Remap Consulting has a proven track record of supporting pharmaceutical and biotechnology companies with price optimisation, price strategy, and launch implementation. Contact us to find out how we can help with the price and reimbursement of your therapy.
References
- European Federation of Pharmaceutical Industries and Associations. Shifting the paradigm for ATMPs: Adapting reimbursement and value frameworks to improve patient access in Europe. European Federation of Pharmaceutical Industries and Associations. Accessed 15/08/25, https://www.efpia.eu/media/636632/atmps-white-paper-cell-and-gene-therapies-related-market-access-issues.pdf
- European Medicines Agency. Advanced therapy medicinal products: Overview. European Medicines Agency. Accessed 15/08/25, https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-products-overview
- European Medicines Agency. Legal framework: Advanced therapies. European Medicines Agency Accessed 15/08/25, https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-products-overview/legal-framework-advanced-therapies
- European Medicines Agency. PRIME: priority medicines. European Medicines Agency Accessed 15/08/25, https://www.ema.europa.eu/en/human-regulatory-overview/research-development/prime-priority-medicines
- European Medicines Agency. CAT quarterly highlights and approved ATMPs May 2025. European Medicines Agency. Accessed 26/08/25, https://www.ema.europa.eu/en/documents/committee-report/cat-quarterly-highlights-approved-atmps-may-2025_en.pdf
- Ronco V, Dilecce M, Lanati E, Canonico PL, Jommi C. Price and reimbursement of advanced therapeutic medicinal products in Europe: are assessment and appraisal diverging from expert recommendations? Journal of Pharmaceutical Policy and Practice. 2021/03/19 2021;14(1):30. doi:10.1186/s40545-021-00311-0
- Iglesias-López C, Agustí A, Vallano A, Obach M. Financing and Reimbursement of Approved Advanced Therapies in Several European Countries. Value in Health. 2023/06/01/ 2023;26(6):841-853. doi:https://doi.org/10.1016/j.jval.2022.12.014
- Rejon-Parrilla JC, Espin J, Garner S, Kniazkov S, Epstein D. Pricing and reimbursement mechanisms for advanced therapy medicinal products in 20 countries. Front Pharmacol. 2023;14:1199500. doi:10.3389/fphar.2023.1199500
- Association of the British Pharmaceutical Industry. Establishing payment models that support timely access to ATMPs. Association of the British Pharmaceutical Industry. Accessed 08/09/2025, https://www.abpi.org.uk/media/0ldleloy/abpi-payment-models-position-paper_-2september2021-final-v2.pdf
- Association of the British Pharmaceutical Industry. Optimising data collection to facilitate access to ATMPs. Association of the British Pharmaceutical Industry. Accessed 08/09/2025, https://www.abpi.org.uk/publications/optimising-data-collection-to-facilitate-access-to-atmps/
- Gozzo L, Romano GL, Romano F, et al. Health Technology Assessment of Advanced Therapy Medicinal Products: Comparison Among 3 European Countries. Brief Research Report. Frontiers in Pharmacology. 2021-October-08 2021;Volume 12 – 2021doi:10.3389/fphar.2021.755052
- Jørgensen J, Hanna E, Kefalas P. Outcomes-based reimbursement for gene therapies in practice: the experience of recently launched CAR-T cell therapies in major European countries. J Mark Access Health Policy. 2020;8(1):1715536. doi:10.1080/20016689.2020.1715536
- Orchard Therapeutics. Orchard Statement on Strimvelis®, a Gammaretroviral Vector-Based Gene Therapy for ADA-SCID. Orchard Therapeutics. Accessed 08/09/2025, https://ir.orchard-tx.com/news-releases/news-release-details/orchard-statement-strimvelisr-gammaretroviral-vector-based-gene
- Pagliarulo N. Bluebird, winding down in Europe, withdraws another rare disease gene therapy. BioPharma Dive. Accessed 09/09/2025, https://www.biopharmadive.com/news/bluebird-withdraw-gene-therapy-europe-skysona/608666/
- Bell J. With European approval secured, BioMarin puts roughly $1.5M price tag on hemophilia gene therapy. BioPharma Dive. Accessed 09/09/2025, https://www.biopharmadive.com/news/with-european-approval-secured-biomarin-puts-roughly-15m-price-tag-on-he/630501/