By Any Genes Necessary: Review of Pipeline Developments and Access Hurdles Likely to be Faced By Gene Therapies

OBJECTIVES: The previous 12 months has seen a marked increase in late-stage developments in the gene therapy pipeline, with three gene therapies approved in Europe, and several others nearing regulatory decisions. With the number of gene therapy approvals increasing, there is a clear need to take a step back and consider how to align various stakeholders. By analysing pipeline developments between June 2022 – June 2023, we explore the key themes emerging.

METHODS: We analysed 100 gene therapies currently in clinical development or approved within the previous 12 months, exploring developments & news flow, and categorising each as either green (positive development), amber (limited/no development) or red (negative development). Qualitative mixed methods were used to draw out key themes emerging, considering manufacturer and payer perspectives.

RESULTS: Our analysis found positive developments for 26 of the 100 gene therapy assets, limited/no developments for 38 of the 100, and negative developments for 36 of the 100 gene therapies. Some of the key themes emerging include issues with agreeing a sufficient evidence package in ultra-orphan conditions, concerns around durability of effect, the balance of benefit:risk and implications for evidence sufficiency, and challenges achieving reimbursement and uptake for recently launched gene therapies

CONCLUSIONS: Recently approved gene therapies demonstrate the challenges that treatments with a high-cost upfront and promise of benefits over the long term can face. To avoid further situations like Zynteglo’s withdrawal from Europe, it will be important for manufacturers and payers to align on how best to approach key challenges, balancing out the incentives to develop innovative therapies with budget constraints at the national level. Where multiple gene therapies are targeting ultra-orphan conditions, there is likely to be a winner takes all outcome for the first entrant.