A €3 million invoice for a single infusion can dazzle as easily as it alarms. Gene therapies such as Libmeldy (≈€2.9 million) and Hemgenix (≈€3 million) have reset the ceiling on drug prices, while “routine” chimeric antigen receptor T-cell (CAR-T) launches still debut just below €0.4 million. Yet the promise these Advanced Therapy Medicinal Products (ATMPs) offer is no less ambitious: one dose, lifelong benefit.
That promise has not insulated them from market reality. Of the 29 ATMPs authorised in the EU by May 2025, roughly one-third have since been withdrawn or suspended – most for commercial or access reasons rather than safety concerns.1 Bluebird bio’s retreat with Zynteglo and Skysona remains the emblematic case: both therapies cleared regulators, then vanished within a year when reimbursement talks stalled.2
When health systems cannot accommodate the price-evidence imbalance, patients are pushed toward ad-hoc fixes such as crowdfunding campaigns or controversial manufacturer-run lottery-style access schemes.3
These examples expose the structural barriers that keep uptake curves for many ATMPs stubbornly flat. Three persistent fault-lines run through every ATMP launch:
- Clinical durability uncertainty
- Budget impact and cash-flow mismatch
- Health system implementation frictions
ATMPs: why traditional pricing and reimbursement models break down
Clinical durability uncertainty
Launch packages for ATMPs typically include single-arm trials, small patient numbers and are heavy on surrogate endpoints. Among EU-approved ATMPs in 2021, the median pivotal-trial enrolment was just 75 patients; 56% of studies were single-arm and 91% were open-label.4 Consequently, long-term durability is inferred rather than observed. Moreover, median follow-up periods are often deemed insufficient for assessing response maintenance and long-term safety.5
Traditional cost-effectiveness models assume robust comparative evidence – an assumption that collapses when faced with the data-light evidence dossiers typical of ATMP launches. The long-term outcomes supported by registry data become crucial for the assessment, yet the registry infrastructure remains uneven.
In some countries, registries are already linked to CAR-T reimbursement, such as Italy’s National Medicines Agency (AIFA)’s CAR-T, France’s DESCAR-T and Spain’s VALTERMED. However, in many other EU markets and across most indications, robust national registry platforms are absent, leaving manufacturers to finance bespoke follow-up studies.6
Budget impact and cash-flow mismatch
A central impediment to demonstrating the value of high-priced ATMPs is the temporal mismatch between their substantial upfront cost and the long-term horizon over which benefits—and any resulting cost offsets—materialise.6
- Cash-flow mismatch: Most European health systems still operate within annual or triennial spending envelopes that cannot accommodate one-off invoices of £1–3 million, even when lifetime cost-offsets imply favourable cost-effectiveness
- Absence of comparators: ATMPs that address severe, previously untreated conditions face even stricter scrutiny at health-technology assessment (HTA), because the lack of a standard of care leaves no costs to offset against the new product’s price
- Discounting effects: Conventional HTA discount rates of 1.5–3.5% per annum further erode the present value of benefits expected to accrue decades after a single infusion, thereby underestimatinglong-term value
- Launch-cohort dynamics: In ultra-rare diseases, once-in-a-lifetime therapies rapidly clear pent-up demand, concentrating expenditure into the first budget cycle and magnifying fiscal pressure.
Taken together, these factors undermine the ability of traditional cost-effectiveness models to demonstrate value for money. Classic tools, such as simple discounts or volume caps tackle price but not timing or uncertainty. European payers are therefore piloting a spectrum of innovative payment models (summarised in Table 1).6
| Payment Model | What It Is | Pros | Implementation Asks |
|---|---|---|---|
| Coverage with Evidence Development | Temporary reimbursement granted on the condition that the pre-defined post-launch data for a reassessment will be collected. | Unlocks early patient access while real-world outcomes accrue; creates a “stop-go” decision point that can raise, or lower price based on the evidence. | A national registry or equivalent platform that can capture agreed-upon endpoints; funding for follow-up tests; and clear rules on what constitutes sufficient evidence at reassessment. |
| Outcomes-Based Agreements | Payment (or rebate) is triggered by individual patient results, such as pay-for-response, survival milestones, or warranty-style refunds. | Aligning spending with real-world performance and rewarding durable benefits can raise the probability that an ATMP meets cost-effectiveness thresholds. | High-quality, timely clinical data; legally robust definitions of “success” and “failure”; dispute-resolution and audit processes; resourced hospital/admin staff to manage data flow. |
| Spread payments / annuities | The multi-million-pound price is broken into smaller instalments over several years. | It matches cash outflow to the timing of patient benefit and cushions annual budgets, especially for large prevalent cohorts. | Accounting treatment that treats instalments as operating expenditure, not year-one debt; multi-year budget flexibility or dedicated funds; credit-risk sharing if a payer defaults. |
| Subscription models | Payer pays a fixed annual or multi-year fee for unlimited (or capped) patient access. | Gives expenditure certainty, encourages rapid treatment of backlogs, and can de-risk epidemiological surprises. | Needs a transparent eligible-patient definition, mechanisms to monitor volume drift, and negotiation of fair “all-you-can-treat” pricing. |
| Expenditure caps | Total spending is capped; any revenue above the ceiling is rebated. | Simple to administer; shields payers from runaway uptake while giving manufacturers headroom to expand access. | Real-time sales tracking, and transparent reconciliation rules. |
The system-readiness problem
Limited centre capacity, immature outcome registries and divergent revenue-recognition rules may hinder the practical rollout of even well-designed payment models. Because ATMPs need specialist facilities to screen candidates, perform cell handling and deliver complex after-care, a shortage of accredited sites can strand eligible patients on waiting lists and create geographic inequities.7
Another issue is fragmented negotiation frameworks, with no shared terminology, evidence standards or model clauses, draw out managed-entry talks and increase transaction costs, while national registries vary widely in coverage, governance and data quality, making it hard to generate consistent evidence required for outcome-linked payments.6,8
Conclusion
Europe’s experience with ATMPs shows that the headline price alone is only one part of the access equation; the binding constraints are timing, uncertainty and system readiness.
Coordinated, early collaboration among regulators, payers and manufacturers is therefore essential. As ATMPs enter the EU Joint Clinical Assessment (JCA) process from January 2025 onward, the mechanism may foster a more unified European approach to evidence expectations, post-launch data collection and registry interoperability.9 Against that backdrop, pipelines must be aligned with fit-for-purpose access tools such as, outcome-based agreements for high uncertainty, coverage-with-evidence development where natural-history data exist, and budget caps for large populations. Robust registries are needed to generate verifiable long-term outcomes, and multi-year payment obligations should be structured under accounting rules that treat them as service contracts rather than public debt.
ATMPs expose the fragility of the traditional reimbursement architecture, yet they also supply the impetus to modernise it. Whether that modernisation succeeds will depend on Europe’s ability to convert this impetus into coherent, data-driven reimbursement pathways that secure timely patient access while safeguarding health-system sustainability. Remap Consulting’s expert team can assist you in navigating these challenges – from supporting ATMP launch implementation and price optimisation to customised price and market access training for your team. Contact us at contact@remapconsulting.com to discover how we can accelerate your therapy’s journey to patients.
References
- CAT quarterly highlights and approved ATMPs. May 2025 https://www.ema.europa.eu/en/documents/committee-report/cat-quarterly-highlights-approved-atmps-may-2025_en.pdf
- Bluebird Withdraws Gene Therapies in Europe as it Winds Down Operations. October 22, 2021 Therehttps://globalgenes.org/raredaily/bluebird-withdraws-gene-therapies-in-europe-as-it-winds-down-operations-there/
- Verbeken G, Convents L, Delmotte N, Draye JP, et al. Current State-Of-Play of the EU Advanced Therapy Medicinal Product (ATMP) Field, With an Emphasis on Belgian Human Cell and Tissue Products. Wound Repair Regen. 2025 May-Jun;33(3):e70039. doi: 10.1111/wrr.70039.
- Iglesias-Lopez C, Agustí A, Vallano A, Obach M. Methodological characteristics of clinical trials supporting the marketing authorisation of advanced therapies in the European Union. Front Pharmacol. 2021;12:773712. doi:10.3389/fphar.2021.773712
- Reimbursement of CAR-T cell therapies in Europe: Key challenges from precedents and lessons for the future. ISPOR 2023 https://www.ispor.org/docs/default-source/euro2023/clement-francois2023reimbursement-of-car-t-cell-therapies-in-europe-key-challenges-from-precedents-and-lessons-for-future132523-pdf.pdf?sfvrsn=817579dc_0
- Unlocking access to future ATMPs in the UK. Comparing international approaches. ABPI 2024 https://www.abpi.org.uk/media/gtoa2ygp/abpi_unlocking_atmps_uk_report.pdf
- Greco A, Frederik GWJ, Hooft L, Ten Ham RMT. A systematic review of challenges and opportunities in the implementation of managed entry agreements for advanced therapy medicinal products. Clin Ther. 2025;47:e16-e26
- Alliance for Regenerative Medicine; Dolon August 2023. Innovative Contracting for ATMPs in Europe: Recent Learnings From the Manufacturer Experience
- New EU rules for health technology assessments become effective. EMA January 2025 https://www.ema.europa.eu/en/news/new-eu-rules-health-technology-assessments-become-effective