Can high-cost drugs be good value? The case of Casgevy for sickle-cell disease and beta-thalassemia

People with sickle-cell disease lack the ability to produce normal haemoglobin, a crucial protein for transporting oxygen in red blood cells. This deficiency leads to the formation of deformed red blood cells that may obstruct blood vessels, leading to severe pain episodes and, in some cases, organ failure. Beta-thalassemia is another genetic disorder characterized by the inability to produce normal haemoglobin. Beta-thalassemia leads to severe anaemia, excessive iron in the body, and delayed growth. Sickle cell disease primarily affects individuals with African heritage, while beta-thalassemia mostly affects people with Mediterranean, south Asian, southeast Asian, and Middle Eastern heritages.

Casgevy (exagamglogene autotemcel or “exa-cel”), a new medicine utilizing CRISPR gene-editing, targets and edits variant forms of genes in bone marrow stem cells that are associated with sickle cell disease and β-thalassemia. The treatment enables the production of functional haemoglobin and can provide profound, life-changing long-term benefits for individuals with these conditions. For example, a single arm trial administered Casgevy to 45 patients suffering from severe sickle cell disease. Of 29 patients followed-up until interim results could be determined, 28 experienced a period of at least 12 consecutive months without vaso-occlusive crisis episodes[i], which causes severe pain and are the biggest driver of emergency hospitalizations for sickle cell disease patients.

Casgevy received licensing authorisations in a number of countries and regions at the end of 2023, including by the United Kingdom’s Medicines and Healthcare products Regulatory Agency United in November, and by United States Food and Drug Administration (FDA) and the European Medicines Agency in December. However, a major challenge to the wider use of Casgevy will be its high cost. While information on list prices is limited, there are reports that the cost in the United Kingdom could be over £1.5m per patient and $2.2m per patient in the United States[ii][iii].

One reason for this cost is the complexity of treatment, since the patient’s stem cells are modified before they are returned back into the body. The treatment process is gruelling and time-consuming for patients, requiring stem cell collection, blood transfusions, chemotherapy, transplantation, and extended hospital stays[iv].  

A more subtle influence on the likely cost of Casgevy pertains to its effectiveness. Since this therapy may be curative for most or all people taking it for either the sickle cell or beta-thalassemia indications, significant future costs are avoided in individuals who would otherwise experience severe illness and associated treatment costs. More importantly from the perspective of the individual patients, the extent of improvements in quality of life, life expectancy and capacity to participate fully in all activities of life can be drastic.

How should one assess whether the value of such a high-cost drug is “worth it” to a health system? This is one of the core questions addressed on the “Economics of Healthcare” course. Economic evaluation is one of the three broad topics covered in the course (alongside sessions in healthcare financing and methods to evaluate non-randomized public health interventions), and offers a means of answering these types of questions in a structured and evidence-based manner.

For example, accounting for the high direct costs of Casgevy is obviously important, but on the other side of the equation it is important to balance these against the future costs avoided by administering a potentially curative intervention. Likewise, value is a function of the health benefits derived by patients, and evidence from initial trial data indicates that these benefits could be very substantial. However, this must again be assessed against the health benefit per pound spent that the health system might expect to gain from spending on other interventions in other disease areas. The costs of the drug therefore cannot be considered in isolation from its benefits, but this ratio of cost to benefit must also be assessed in terms of the wider impacts on the health system.

Lectures and practice exercises on the course will take students through the rationale for different approaches to economic evaluation, and will involve both practical, hands-on exercises involving the mechanics of these calculations, but will also consider the wider ethical considerations involved. For example, should the impact on carers of patients with beta-thalassemia be accounted for when considering its benefits? The burdens of sickle-cell disease are often most significant in lower-income countries, or on individuals with lower incomes in wealthy countries. Can and should these considerations influence the price at which therapies are offered to different patients and different countries? Does the innovative nature of Casgevy, as the first approved CRISPR treatment for disease, merit special treatment to encourage the development of other new medicines? The course will also therefore examine how different approaches to priority setting ultimately influence which effective therapies are made available to patients and health systems, and at what price.