NICE rejects gene therapy Zynteglo


Following NICE draft guidance rejecting Zynteglo, Eleanor Butler, Consultant at Lightning Health explores why the beta thalassaemia treatment is not recommend for routine NHS funding.

NICE has rejected bluebird bio’s gene therapy, Zynteglo, for patients with transfusion-dependent beta-thalassaemia (TDT). Zynteglo did not meet NICE’s end-of-life criteria but was considered innovative, so an ICER closer to £30,000 per QALY gained was considered acceptable. The most plausible ICER, using the committee’s preferred assumptions, for Zynteglo was estimated to be considerably higher than £30,000 per QALY gained and associated with a high level of uncertainty relating to longer-term clinical effectiveness (including evidence from a small number of patients with limited follow up of just over 5 years). 

Zynteglo had been routed through a Single Technology Appraisal (STA) process, prompting concerns that costs and benefits would not be reviewed as adequately as through the Highly Specialised Technologies (HST) programme, limiting the cost-effectiveness threshold and presenting a more challenging assessment framework for a therapy with a one-off high upfront cost.

Bluebird bio proposed a 1.5% discount rate for costs and benefits, which was not accepted, and the Committee concluded that a 3.5% discount rate should be used in line with the methods of technology appraisal. The use of a non-reference-case discount rate may be considered when treatment restores people who would otherwise die or have a very severely impaired life to full or near full health and this is sustained over a very long period (normally at least 30 years). These criteria were not considered to be met as the committee noted that some people who have treatment with Zynteglo do not see a reduction in transfusions, or transfusion independence. Additionally, TDT has other management options apart from hematopoietic stem cell transplantation (HSCT) and the Evidence Review Group (ERG) highlighted that the indicated population are likely to have a life-expectancy of more than 45 years even without Zynteglo. It was therefore concluded that the criteria for using a 1.5% discount rate for costs and benefits were not met. 

NICE proposes that the guidance on this technology is considered for review by the guidance executive 3 years after publication. This allows for consideration of data from bluebird bio’s long-term follow-up study, LTF-303.

To many this comes as a surprise considering approval for reimbursement in both France and Germany. An ASMR of III was awarded in France with the establishment of a patient registry to inform reassessed within a maximum of 3. In Germany Zynteglo has been awarded a non-quantifiable added benefit and bluebird bio have entered into performance-based payment agreements with multiple statutory health insurance funds. It is reported that the company had also prepared a commercial arrangement for NICE, which would have applied in the event of a positive recommendation. 

Is it that Zynteglo is not cost-effective or is it that the NICE cost-effectiveness threshold for a potentially transformative clinical development is too low? In context of EU access, there has been flexibility to negotiate innovative funding models at sickness fund level in Germany and in France we have seen the adaptability of HAS to consider post-launch RWE generation to address uncertainty with the data available at launch. Based on the NICE recommendations for Zynteglo, it appears that the current methods do not afford the same opportunity to grant patient access to potentially high value clinical developments, with innovative access models to address data uncertainty at launch. How NICE choose to address this need to balance access to innovation with mitigating risk and uncertainty will be a critical factor to monitor within the ongoing NICE methods review process. 




Article published 12 February 2021.