Nermina Ferizovic | Health Economics Expert

For the next blog post in the series where I review papers published as part of the “Economics of Gene and Cell Therapies” in PharmacoEconomics, I will review: ‘Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States’ found at the following link: https://link.springer.com/article/10.1007/s40273-024-01385-9. 

Individuals with sickle cell disease experience chronic anaemia, vaso-occlusive events (VOE), strokes, infections and swelling due to genetic mutations. This leads to reduced quality of life and a lower life expectancy. Lovo-cel is a genetic therapy using autologous haemopoietic stem cells transduced with a lentiviral vector containing a modified beta-globin gene. The authors conducted this study to support discussions on value and affordability of advanced therapies. 

The authors developed a patient simulation model to assess the cost-effectiveness of lovo-cel – a one-time therapy – versus standard of care in patients with sickle cell disease from a societal (including caregiver quality-of-life impacts and indirect costs related to productivity loss and unpaid caregiving) perspective and the third-party payer in the United States. The patient population was limited to those ≥ 12 years with ≥ 4 VOEs in the past 24 months with efficacy and safety data based on the pivotal phase II trial. The literature informed inputs not available from the trial such as costs. The authors sought advice from independent clinical and economic advisors to validate their approach and spoke with patients with sickle cell. Uncertainty was also assessed using probabilistic sensitivity analysis.  

The authors found that modelled patients receiving the one-time therapy lived 23.84 years longer on average compared to those modelled to receive standard of care with gains in quality of life and a reduction in direct medical costs. However, there was an increase in overall costs due to lovo-cel acquisition costs. In the societal perspective, there was a reduction in indirect costs and improved caregiver quality of life and life expectancy. Lower incremental cost-effectiveness ratios were generated when a societal perspective was taken compared to the third-party payer perspective. 

The study uses common health economic methodologies to add to the literature examining the cost-effectiveness of gene therapies. A heterogenous patient population using a patient simulation model and carefully considers the relevant comparators for the modelled patient population with a lifetime time horizon taken. The inclusion of patient and clinician input undoubtedly improved the validity of the cost-effectiveness analysis. Finally, the study demonstrates that there is large uncertainty when assessing the economic value of advanced therapies and that a societal perspective results in improved incremental cost-effectiveness ratios. 

A couple of key points arise from this study. A key issue with modelling the clinical and economic impacts of gene therapies is the uncertainty surrounding their long-term clinical benefits with the authors arguing that the ‘clinician-informed framework is novel to their analysis and is intended to provide a balanced view of the potential long-term clinical benefits following lovo-cel therapy’. However, the consideration of clinical input in model development is not novel and in this instance, it may well have been better to have employed an expert elicitation methodology or at least provided a justification for their approach. As acknowledged by the authors, real-world evidence studies would support assumptions around long-term real-world efficacy/safety and would be necessary to reduce uncertainty especially as clinical inputs have a large impact on the cost-effectiveness results.  

The authors argue that other value elements such as value of hope should be accounted for in cost-effectiveness analyses of gene therapies; in a previous blog post I have argued that this is an extension of clinical benefits coupled with risk preference meaning that this would be a double count thereby bias results. 

Related to this point is the impact of the inclusion of societal impacts such as productivity and caregiver burden. Like similar analyses, this study demonstrates that the inclusion of societal burdens can improve the cost-effectiveness of gene therapies; however, this is of little significance to healthcare payers who are unlikely to realise the benefits of reduced societal impacts on their future budgets although they are expected to pay the large costs for its procurement. This is a common discussion point when there are calls for a societal perspective to be taken in healthcare decision making but is less commonly discussed during discussions of who should pay for gene therapies. Whether or not an economic assessment is fair, who ultimately is paying for the treatment should be considered. Given the high costs of these treatments combined with their broad benefits, there should be more consideration given to how and by whom these treatments are funded to support a ‘fairer’ economic assessment. 

In summary, this study contributes to the growing literature on the cost‑effectiveness of gene therapies, although its findings largely align with existing discussions on the economics of advanced therapies.