Pricing and reimbursement of cell and gene therapies in Europe: outcomes and novel approaches



The European landscape has seen both approvals and withdrawals of cell and gene therapies in recent years. Most withdrawals seem to be due to a lack of commercial viability for the manufacturers, rather than safety concerns. EU payers face challenges in assessing the clinical value of these novel treatments due to the limited data packages at launch, impacting pricing and reimbursement outcomes. However, the launches of Kymriah and Yescarta, two chimeric-antigen receptor T (CAR-T) cell therapies, demonstrate how outcomes-based agreements can be used to secure reimbursement for cell and gene therapies in Europe.

A lack of commercial potential is leading to product withdrawals

As of August 2022, there have been 19 approved cell and gene therapies in Europe1. Most recently, Upstaza and Roctavian have been approved for the treatment of Aromatic l-amino acid decarboxylase (AADC) deficiency and severe haemophilia A, respectively. Yet the last decade has also seen product withdrawals from the European market, such as Bluebird’s Zynteglo and Skysona.

Both Bluebird’s products were approved by the European Medicines Agency (EMA) in the first half of 2021, however by the end of the year they had been withdrawn from the European market. An initial list price of $1.8 million (€1.77 million) was set by Bluebird for Zynteglo, indicated for severe β-thalassemia. Germany however countered with an initial price of $790,000 per patient (€777,000)2. Subsequent failure to reach an agreement in pricing negotiations led to the manufacturer withdrawing the product, reflecting that being granted approval does not guarantee commercial success.

Clinical uncertainty creates a need for risk-sharing approaches between companies and payers

The EMA has implemented a specific framework for the evaluation of cell and gene therapies. However, most health technology assessment (HTA) bodies have not done the same. For example, in its recent methods update NICE found that there was no case to make specific provision for ATMPs3.

Cell and gene therapies come to market with limited clinical data, for various reasons including their indication for serious, very rare diseases with few or no comparative treatments currently available. Usually, the clinical trials for these products are short, non-comparative and based on surrogate endpoints, while their effects are expected to be life-long. This creates considerable uncertainty for payers in assessing the size of the clinical benefit for cell and gene therapies compared with standard of care, and how long that benefit lasts. The high prices of these products means that companies and payers are increasingly exploring innovative payment approaches to share risk while facilitating timely patient access.

Novel approaches that allow demonstration of real-world value are required

The uncertainty associated with cell and gene therapies can be managed through adopting novel approaches to pricing and reimbursement. The entry of Kymriah and Yescarta into the EU4 and UK markets highlights how real-world evidence (RWE) is becoming a powerful tool to demonstrate the value of cell and gene therapies in a clinical setting.

The launch of Kymriah in Germany was secured through a first-of-its-kind outcomes-based agreement. Under this agreement, Novartis will partly reimburse the cost of Kymriah, €320,000 per patient (pending negotiations), in the event a patient dies due to their blood cancer within an agreed time frame4. Other innovative reimbursement schemes such as staged payments tied to patient outcomes were employed in Spain and Italy, where payments are conditional on treatment success6. In Spain, the Valtermed system is used to collect data for each therapy and assess response to treatment at time horizons of 12 and 18 months. In Italy, although both companies will receive payments in 3 instalments, the time horizons are slightly different. Whereas Novartis will be paid at time of infusion, 6 months and 12 months if a sustained response is demonstrated with Kymriah, the first payment for Yescarta is scheduled at 6 months6. This implies that Gilead will absorb more risk in its scheme (as it is not paid at the initial infusion), highlighting the variation of schemes with the extent of uncertainty in supporting evidence.

In the UK, Gilead negotiated a discount with NHS England to secure access via the Cancer Drugs Fund for Yescarta, which allowed real-world evidence to be collected from the Systematic Anti-cancer Therapy (SACT) dataset, as well as longer term data from the ZUMA-1 clinical trial. This data collection period ended in February 20227, and as such Yescarta will soon be re-appraised by NICE for its suitability for routine commissioning. Kymriah is also available through the Cancer Drugs Fund, with a data collection period anticipated to conclude in June 2023 based on the pivotal ELIANA study8, followed by a re-appraisal by NICE. In France, access to Kymriah and Yescarta was made available through the early access program ‘Temporary Authorisation for Use’ (ATU). Real-world data collection was limited in the ATU, only 17 patients received Kymriah6. For both Kymriah and Yescarta, the Transparency Committee (TC) requested further long-term data should be collected to address uncertainties in the data and they were therefore reimbursed on the condition that a CAR-T specific registry be established to allow this6.

The unique challenges that cell and gene therapies present therefore provide an opportunity to shift approaches away from traditional pricing and reimbursement approaches to greater use of real-world evidence to mitigate uncertainties, and payment schemes to centred on treatment success.


Cell and gene therapies launched in Europe to date have had varied pricing and reimbursement success. The clinical uncertainty resulting from limited data packages can make securing commercially viable outcomes for manufacturers a challenge. To support patient access to the important benefit these treatments can achieve, work should continue on implementing novel reimbursement approaches that recognise the unique value of cell and gene therapies. The experience of recent launches to the European landscape suggests that the potential for outcomes-based reimbursement and coverage with evidence development schemes as an opportunity to demonstrate the real-world value of these therapies should be explored further.


  1. Iglesias-Lopez, C., Agusti, A., Vallano, A., Obach, M., 2021. Current landscape of clinical development and approval of advanced therapies. Methods & Clinical development, 23, pp.606-618, DOI:
  2. Bluebird, winding down in Europe, withdraws another rare disease gene therapy Accessed September, 2022.
  3. Methods, Processes and topic selection for health technology evaluation: proposals for change. NICE. Accessed September, 2022
  4. Detela, G. & Lodge, A. 2019. EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation. Molecular therapy, 13(4), pp. 205-232.
  5. van Overbeeke, E., Michelsen, S., Toumi, M., Stevens, H., Trusheim, M., Huys, I. and Simoens, S., 2021. Market access of gene therapies across Europe, USA, and Canada: challenges, trends, and solutions. Drug discovery today, 26(2), pp.399-415.
  6. Jesper Jørgensen, Eve Hanna & Panos Kefalas (2020) Outcomes-based reimbursement for gene therapies in practice: the experience of recently launched CAR-T cell therapies in major European countries, Journal of Market Access & Health Policy, 8:1, DOI: 10.1080/20016689.2020.1715536
  7. Axicabtagene ciloleucel for treating diffuse large Bcell lymphoma and primary mediastinal B-cell lymphoma after 2 or more systemic therapies [TA559]. Cancer Drugs Fund, Managed Access Agreement (2019). NICE.
  8. Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years [TA554]. Cancer Drugs Fund, Managed Access Agreement (2018). NICE.
  9. Autologous anti-CD19-transduced CD3+ cells for treating relapsed or refractory mantle cell lymphoma [TA677]. Cancer Drugs Fund, Managed Access Agreement (2021). NICE.

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