Gene Therapy Reimbursement
MYO Health - Katerina Pilou
Gene therapy aims to correct the underlying genetic defects through the replacement or addition of genetic material. Gene therapies have been developed for chronic genetic diseases such as haemophilia and spinal muscular atrophy, as well as for certain types of cancer. Unlike conventional treatments that aim to treat symptoms, gene therapies have the potential to provide a cure. They are very expensive treatments but require only one or two doses, unlike current therapies that require continuous lifelong treatment.
There are many challenges associated with the reimbursement of gene therapies:
a) Gene therapies are very expensive due to the complexity of the R&D and manufacturing processes. Indicatively, the manufacturer’s price of reimbursed gene therapies in Greece ranges from 270,000 to 1.8 million per administration.1
b) as most gene therapies target rare diseases, their clinical trials are usually limited to a small number of patients, while some consist of a single treatment arm (single-arm trials).2 Further, gene therapies are aimed at patients with chronic, lifelong diseases and the period of clinical observation is still limited, so it is uncertain whether their effectiveness will diminish over time, resulting in the need for further treatment. 2
c) the lack of clinical data and the uncertainty regarding the long-term efficacy of gene therapies make it challenging to model these therapies and thus to estimate the incremental cost-effectiveness ratio (ICER). 1
d) utility values represent a crucial element in cost-effectiveness analyses. However, due to the rarity of the diseases targeted by gene therapies, utility values from representative patient samples may not be available in the literature, thus not accurately reflecting patient experience. 1 Furthermore, the additional benefit that patients may receive when they believe that their disease is fully cured is not sufficiently appreciated. This argument has also been made in the context of vaccination, as the benefit is received immediately, rather than at some future point. 1,3
e) there is a growing body of opinion that the value aspects of gene therapies justify a higher willingness to pay threshold. 1,3
f) Drummond et al. propose a lower discount rate for gene therapies, given that gene therapies are likely to be associated with high one-off costs, yet may also lead to lifelong benefits after a single dose. 1,3
The aforementioned challenges have necessitated the development of novel and creative compensation mechanisms. 1 As an example, in France the “Coverage with Evidence Development” (CED) approach permits early access (with reimbursement) to promising gene therapies prior to full marketing authorization, contingent upon further data collection to confirm their efficacy and ensure continued reimbursement.4,5
Italy and Spain have implemented a reimbursement model known as “Outcomes-Based Reimbursement (OBR)”, which directly correlates the reimbursement of gene therapy to the clinical course of each individual patient.6,7 In accordance with this model, marketing authorisation holders (MAHs) may be obliged to reimburse a proportion of the cost of the gene therapy administered if it fails to achieve the predefined therapeutic target, thereby reducing the financial risk for the payer.8,9
England and Scotland utilize both Coverage with Evidence Development (CED) and Outcome-Based Reimbursement (OBR) approaches, along with various patient access schemes. For instance, gene therapies for non-Hodgkin lymphoma and for acute lymphoblastic leukaemia were reimbursed by NICE (Cancer Drugs Fund – CDF) on the condition that additional data would be collected and submitted for future reimbursement decisions and price reassessments.10,11
In Greece, according to the president of the Association of Rare Diseases Greece, there are “special early access programs” in which “the state can enter into an agreement with the pharmaceutical company with the objective of facilitating access to gene therapies for a limited number of patients for a specified period of time”.12
Five gene therapies are included in the positive list and have received a reimbursement price in Greece: Zolgensma® for Spinal Muscular Atrophy (SMA), Luxturna® for patients with an inherited retinal disease (IRD) due to a mutation in their RPE65 gene, Yescarta® for two types of non-Hodgkin lymphoma, Kymriah® for B-cell acute lymphoblastic leukemia and Tecartus® for acute lymphoblastic leukaemia and mantle cell lymphoma.
At the 9th annual HTA conference, Dr. Christos Georgakopoulos, Market Access Director of the Hellenic Association of Pharmaceutical Companies (SfEE), presented data showing that, on average, only 39% of gene therapies are available to EU patients. Greece had the lowest availability rate among the surveyed countries, with just 11%. Additionally, Greece had the longest time to availability for gene therapies, averaging 900 days, which is significantly longer compared to the availability times for other drug classes in the country.
Gene therapies offer the potential for significant long-term health benefits. However, in order for them to be accessible to patients, it is necessary to make progress in the regulatory framework governing their reimbursement.
- van Overbeeke, E., Michelsen, S., Toumi, M., Stevens, H., Trusheim, M., Huys, I., & Simoens, S. (2021). Market access of gene therapies across Europe, USA, and Canada: challenges, trends, and solutions. Drug discovery today, 26(2), 399–415. https://doi.org/10.1016/j.drudis.2020.11.024
- Besley, S., Henderson, N., Towse, A. & Cole, A. (2022) Health Technology Assessment of Gene Therapies: Are Our Methods Fit for Purpose?. OHE Contract Research. Available from https://www.ohe.org/publications/health-technology-assessment-gene-therapies-are-our-methods-fit-purpose/
- Drummond MF, Neumann PJ, Sullivan SD, Fricke FU, Tunis S, Dabbous O, Toumi M. Analytic Considerations in Applying a General Economic Evaluation Reference Case to Gene Therapy. Value Health. 2019 Jun;22(6):661-668. doi: 10.1016/j.jval.2019.03.012. Epub 2019 May 17. PMID: 31198183.
- John, Hutton., Paul, Trueman., C., Henshall. (2007). Coverage with evidence development: an examination of conceptual and policy issues.. International Journal of Technology Assessment in Health Care, doi: 10.1017/S0266462307070651
- Jørgensen, J., & Kefalas, P. (2021). The use of innovative payment mechanisms for gene therapies in Europe and the USA. Regenerative medicine, 16(4), 405–422. https://doi.org/10.2217/rme-2020-0169
- Ildikó, Ádám. (2022). Outcome-based reimbursement in Central-Eastern Europe and Middle-East. Frontiers in Medicine, doi: 10.3389/fmed.2022.940886
- Liang, Xu., Hongmin, Li., Huijun, Zhao. (2022). Outcome-Based Reimbursement: The Solution to High Drug Spending?. Manufacturing & Service Operations Management, doi: 10.1287/msom.2021.1051
- (2023). An Economic Analysis of Outcomes-based Payment in Healthcare. Policy Perspectives, doi: 10.4079/pp.v30i0.05
- Paula, Lorgelly., Jack, Pollard., Jack, Pollard., Patricia, Cubi-Molla., Amanda, Cole., Duncan, Sim., Jon, Sussex. (2020). Outcome-Based Payment Schemes: What Outcomes Do Patients with Cancer Value?. The Patient: Patient-Centered Outcomes Research, doi: 10.1007/S40271-020-00430-X
- Iglesias-López C, Agustí A, Vallano A, Obach M. Financing and Reimbursement of Approved Advanced Therapies in Several European Countries. Value Health. 2023 Jun;26(6):841-853. doi: 10.1016/j.jval.2022.12.014. Epub 2023 Jan 13. PMID: 36646280.
- 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 Jan 15;8(1):1715536. doi: 10.1080/20016689.2020.1715536. PMID: 32082514; PMCID: PMC7006635.
- https://www.euractiv.gr/section/koinoniki-eyropi/special_report/nomothetiko-keno-stin-ellada-gia-tin-prosvasi-stis-gonidiakes-therapeies/