Why Gene Therapies Keep Hitting Price & Access Roadblocks 

The pricing benchmark has shifted faster than systems have adapted. In the UK, prices for one-time treatments like gene therapies have reached unprecedented levels. The National Institute for Health and Care Excellence (NICE) lists onasemnogene abeparvovec (Zolgensma) at £1.79 million for a single dose, while atidarsagene autotemcel (Libmeldy) is recorded at £2.88 million. These therapies’ prices require health systems to commit very large sums up front, often before lifetime benefits are fully proven.¹ 

Rather than redesigning methods to accommodate one-off curative payments, many systems have tightened affordability rules. England’s Budget Impact Test is now set at £40 million per year (any of the first three years), and Canada’s national agency provides a standard budget-impact analysis template that centres near-term spend.^2,3 

The result is friction. Manufacturers are seeking early, premium prices without mature data. Payers, meanwhile, are defending annual budgets with tools built for chronic treatments, not one-time cures. 

This article reviews past gene therapy launches to understand how misaligned incentives and affordability constraints shaped access and explores whether those same challenges persist in today’s market. 

Misalignment between one-time costs and fragmented budgets

Drug spending is climbing faster than overall health funding. The median launch price of a new medicine in the US has more than doubled in just four years, with rare-disease treatments accounting for almost three-quarters of approvals.⁴ Yet payer tools still lock budgets into one- to three-year horizons, so a therapy can look “cost-effective” over a lifetime while being fiscally impossible to adopt on day one.^2,3 

This structural misalignment has already shaped outcomes. Alipogene tiparvovec (Glybera) was the first gene therapy to hold an EU approval but never achieved routine adoption, and the company let its licence lapse in 2017, citing “lack of demand”.⁵ Bluebird Bio and other developers have also found Europe commercially challenging and have scaled back or exited activities there. These failures were not regulatory rejections but commercial and reimbursement failures.^6,7  

There are counter examples where coordinated payer approaches or managed access arrangements unlocked access. Libmeldy secured reimbursement through Beneluxa joint negotiation, and etranacogene dezaparvovec (Hemgenix) reached England under a managed-access/commercial arrangement that ties conditional availability to ongoing evidence generation. These cases show that coordinated purchasing or time-limited coverage plus evidence-generation can bridge the timing/affordability gap.⁸  

HTA frameworks and trade-offs 

HTA frameworks still struggle to reflect long-term value due to uncertainty. For therapies where most of the benefit is expected decades into the future, technical modelling choices like discount rates can have strong impacts. Discounts differ between countries. For example, NICE’s reference case uses 3.5% discounting (with a possible 1.5% non-reference case in tightly defined circumstances), the Pharmaceutical Benefits Advisory Committee (PBAC) traditionally uses 5%, while Canada’s Drug Agencies (CDA) 4th-edition guidance centres on 1.5% as a reference. These discounting differences can shift ICERs substantially when much of the value lies far in the future. ^9-11 

Perspective also differs. Sweden’s TLV emphasises societal aspects (bringing productivity and caregiver effects into scope), whereas many budget-impact processes such as Canada’s focus on 1–3 years, keeping attention on the up-front costs rather than long-term offsets.¹²  

HTA outcomes reflect this tension. NICE’s guidance for both Zolgensma and Libmeldy recognises long-term uncertainty and relies on commercial or managed arrangements when lifetime benefit is plausible but not yet demonstrated.¹  

Ongoing relevance of the challenges 

These challenges are not fading. Top prices are higher than five years ago, and affordability gates are more explicit, so the underlying problems are more acute. HTA bodies and payers are moving away from assuming long-term durability at launch. Instead, they are investing in post-launch evidence systems to manage uncertainty over time.^13,14  

Germany’s Federal Joint Committee (G-BA) now requires certain advanced therapy medicinal products (ATMPs) to include application-accompanying data collection. For example, Hemgenix can only be used in designated centres that contribute outcomes to the national haemophilia registry. Similarly, Scotland’s ultra-orphan pathway and the Italian Medicines Agencies (AIFA) registries mandate time-limited reimbursement tied to real-world data capture and reassessment. These frameworks formalise the idea that access must be earned and maintained based on real-world performance.^15-17 

Even when reimbursement is secured, delivery infrastructure can be a bottleneck: specialised centres, genetic confirmation and multidisciplinary teams concentrate treatment sites and can slow scale-up even where reimbursement is agreed (e.g., NICE’s appraisal of Zolgensma).¹ 

Conclusion

The story across recent launches is consistent: companies are arriving with genuinely transformative therapies but are asking for curative-level prices before curative-level evidence is available. At the same time, health systems are operating under fixed budgets and using tools designed to manage predictable, chronic costs, not large, one-off expenditures with uncertain long-term outcomes.  

This disconnect continues to shape market access for gene therapies. It is why Glybera lapsed, and Bluebird Bio withdrew despite regulatory approvals. 

Where manufacturers credibly share long-term risk and payers deploy flexible mechanisms (joint purchasing, managed access with robust registries), the promise of gene therapy is more likely to translate to routine care. If you’re preparing to bring a gene therapy or other innovative medicine to market and need expert support on pricing, HTA strategy, evidence generation or reimbursement negotiations, Remap Consulting can help, get in touch. 

References

1. National Institute for Health and Care Excellence. HST24: Onasemnogene abeparvovec for treating presymptomatic spinal muscular atrophy. 2023.
2. National Institute for Health and Care Excellence. Guide to the processes of technology appraisal. 2014.
3. Canada’s Drug Agency L’agence des Medicaments du Canada. Budget Impact Analysis Tool. https://www.cda-amc.ca/budget-impact-analysis-tool
4. Reuters, Beasley D. Prices for new US drugs doubled in 4 years as focus on rare disease grows. https://www.reuters.com/business/healthcare-pharmaceuticals/prices-new-us-drugs-doubled-4-years-focus-rare-disease-grows-2025-05-22/
5. European Medicines Agency. Glybera: Expiry of the marketing authorisation in the European Union. 2017.
6. European Medicines Agency. Skysona: Marketing authorisation status. 2021.
7. Fierce Pharma, Dunleavy K. With the pricing situation ‘untenable’ in Europe, bluebird will wind down its operations in the ‘broken’ market. https://www.fiercepharma.com/pharma/situation-untenable-bluebird-will-wind-down-its-operations-broken-europe
8. National Centre for Pharmacoeconomics Ireland. Atidarsagene (Libmeldy®). HTA ID: 21009. 2021;
9. National Institute for Health and Care Excellence. NICE health technology evaluations: the manual. 2022.
10. Canada’s Drug Agency L’agence des Medicaments du Canada. Discounting and the Evaluation of Health Care Programs. 2018.
11. Pharmaceutical Benefits Advisory Committee. Review of base-case discount rate in the PBAC Guidelines. 2022.
12. Government of Canada. Budget Impact Analysis Guidelines. 2020.
13. NHS England. Budget Impact Test threshold consultation – summary of response. 2025.
14. National Institute for Health and Care Excellence. NICE real-world evidence framework. 2022.
15. Gemeinsamer Bundesausschuss. Application-related data collection for etranacogen dezaparvovec (Hemgenix®). 2024.
16. Scottish Government. Ultra-orphan medicines pathway: guidance. 2019.
17. Agenzia Italiana del Farmaco. Monitoring Registers.