Cell and gene therapies: Why new approaches to pricing and reimbursement are needed in Europe

Christophe Hilbert, senior manager of Access, Value, and Evidence Strategy, Europe at bluebird bio explores the problems of pricing and reimbursement for gene and cell therapies in Europe.

At the dawn of gene and cell therapies, it appears that our healthcare systems are not keeping pace with scientific progress. While continuous research and development has led to the rise of a new class of therapies, some of which hold curative promises, healthcare systems continue to rely on processes that were designed for previous generations of chronic treatments when making reimbursement decisions. It is thus crucial to ask whether relying on these legacy processes may put existing innovation at risk, stifling future innovation in Europe and preventing patients from having access to potentially life changing therapies?

Health Technology Assessment and price negotiation: the missing link

For national healthcare systems to evaluate a drug product and its worth, national pricing and reimbursement processes typically consist of two steps: A Health Technology Assessment (HTA), followed by a price negotiation. Simply put, an "HTA measures the added value of a new health technology compared to existing ones". HTAs play a key role in informing the price negotiation. However, in the case of gene and cell therapies, randomised controlled trials, which are regarded by HTA frameworks as the gold standard, may not be feasible or ethical. This means it can be challenging to do an HTA and create a strong link between these two cornerstones of access, leading to situations where the HTA outcome is not factored into the price negotiation – or only loosely linked to it. This inevitably leads to a price that does not accurately reflect the therapy’s true value.

When scientific reality collides with price negotiation

One area where we see this disconnect is in the evaluation of innovative therapies with curative intent by national systems. Whereas regulatory and scientific bodies like the European Medicines Agency consider that the effect of some of these therapies is expected to be life-long, this perspective is not always shared by national healthcare systems. 

Although it is somewhat understandable that healthcare systems may initially struggle to appropriately value therapies with expected life-long effect (there is no scientific data yet which spans human lifetime), it also does not make sense to base decisions on a random time frame (e.g., 15 years) as part of price negotiations. This is especially the case when discounting can be used as a simple financial tool to reflect a life-long effect. 

What you see is what you get: how clinical trials and annual cost considerations get leveraged to chronify diseases

To date, no country has fully adjusted its processes to adequately reflect the peculiarities of gene and cell therapies. In the eyes of some healthcare systems, it is a case of "what you see is what you get". In fact, it is not uncommon to hear that the duration of clinical trials should inform value definitions, whether they are one-time treatments or chronic therapies. This means that the value of a potentially curative one-time therapy in relation to a life-long permanent therapy must therefore be based on the observation period of clinical trials. This also suggests that a life-long effect can only be monetised when the new therapy has been available on the market for a lifetime.

The pharmaceutical industry is often criticised for prioritising profit over public health objectives, investing in chronic treatments instead of new curative therapies. It seems ironic, then, that as one-time therapies reach the market, health systems are measuring value by the duration of clinical trials. This might not only mean the end of one-time therapies; it also implies the continuation of higher cost burdens from the long-term treatment of chronic diseases.

Intrinsic differences between gene and cell therapies

Gene and cell therapies are complex and often conflated, with the differences between them overlooked. However, these differences are critical in understanding mode of action, durability of effect (whether lifelong or not), as well as clinical and economic value. There are also significant differences between gene therapies – including whether treatments take place inside or outside the body, and their delivery method using different types of vectors. All these factors need to be appreciated when assessing value and price.

Prevalence vs incidence: a question of commercial viability

Another issue that healthcare systems must consider when determining value is the characteristics of the patient population.

For example, whereas certain severe genetic diseases have a defined pool of prevalent patients with a lower incidence of new patients, oncology products usually target variable-sized prevalent patient pools with a constant, non-negligible incidence rate. This has important economic implications on commercial viability. Given those therapies aimed at severe genetic diseases will have a pool of prevalent patients to treat but only low incidence of new patients, manufacturer revenues will rapidly decrease as the innovation is applied. The situation is different for oncology products: once an established therapy, revenues are expected to remain steady, or even grow as populations age. This is one of the elements determining the commercial viability of, and future research into, innovative therapies. To interpret the example from the viewpoint of healthcare systems, replace “revenue” by “budget impact”.

Outlook for a better future

While today's pricing and reimbursement processes are still struggling to properly value gene and cell therapies, there is hope. For one, there is acknowledgement of the need to recalibrate current systems across the entire healthcare ecosystem – from industry, trade associations, patient groups, health economists, politicians, and payers. The topic of reform and adapting current HTA systems is being widely debated at national and pan-European levels, and is the focus of many academics and expert health economists working to address barriers such as uncertainty, discount rate, societal value, and budget impact. Hopefully, initiatives such as the EU’s Pharmaceutical Strategy for Europe will help drive this much needed change so that we begin to see a world where gene and cell therapies will consistently become available to patients.

The clock is ticking, however, regarding effective reform, raising concerns over whether gene and cell therapies will ever have broad access in Europe. One question remains: What can be done to accelerate the adjustment of pricing and reimbursement processes to properly value these innovations across Europe and increase the treatment choices available to rare disease patients?