What is the future of precision medicine in the EU?

The field of precision medicine is a complex area with many overlapping definitions and terminologies. Precision medicine is an umbrella term for the treatment and prevention of disease using a combination of drug and diagnostic, considering individual variability in genes, environment, and lifestyle. Manufacturers have found market access to be a significant challenge as countries adapt their existing pricing and reimbursement processes to account for the dual assessment of the drug and accompanying diagnostic. This article will explore the various definitions surrounding precision medicine, and the specific market access considerations for this growing area of research.

Why are payers interested in precision medicine?

Medicine that is truly unique to the patient, allowing for the best possible efficacy with minimal side effects, is often seen as the future of healthcare. The mainstream use of ‘personalised medicine’, where medical treatment is tailored to the individual characteristics of each patient (e.g. stem cell therapy and genome editing/therapy), is still many years away. Nevertheless, there has been growing interest in the widespread use of medicine that is targeted towards a specific subset of best-responding patients. The precision medicine approach, in theory, should broadly appeal to payers: targeting patients who are most likely to respond will allow diseases to be treated more efficiently with less drug wastage and fewer side effects for the patient. However, the implementation considerations, including funding of the diagnostic and treatment of precision medicine complicate the situation, resulting in varying enthusiasm and uptake across the countries.

Common terms used within precision medicine

The terminology related to precision medicine is currently poorly defined, with many common terms that overlap. Some of the terminology that is used include:

  • Stratified medicine: Grouping patients with distinct mechanisms of disease and responses to treatments, allowing identification and development of treatments that are effective for groups of patients
  • Targeted therapies: Treatments which can be selected based on their known ability to target specific genes or proteins associated with the disease

Stratifying subgroups within the patient population usually requires diagnostic tools to identify specific biomarkers. These diagnostic tools, usually in-vitro, are split into two categories.

  • Biomarkers: A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease
  • Companion diagnostic: A device/accessory that is essential for the drug therapy to be used safely and effectively. Included in the regulatory label
  • Complementary diagnostics: A device/accessory that is not essential for the drug therapy to be used, but still aids in the benefit/risk decision making. Not included in the regulatory label

An example of a precision medicine is vemurafenib. Vemurafenib is an oral tyrosine kinase inhibitor of the oncogenic BRAF V600 protein kinase and has UK marketing authorisation for BRAF V600 mutation-positive melanoma. As a requirement, all patients starting treatment on vemurafenib in the UK should have a positive test for the BRAF V600 mutation (using a companion genetic mutation test developed by the same manufacturer).

Market access for precision medicine is complicated by the requirement to prove that the clinical benefit outweighs financial impact

It is the duality of targeted therapies and their associated diagnostics that complicates assessment and market access for precision medicines. Not only must payers assess the clinical and economic effectiveness of the drug, they must do the same for the associated diagnostic. Therefore, for a companion diagnostic to be reimbursed and funded alongside the drug, it is important to generate strong clinical evidence that the use of the diagnostic is linked to improved clinical outcomes for the patient. It is vital for manufacturers to incorporate the patient sub-population identified by the companion diagnostic into the clinical trial design. Looking again at vemurafenib, NICE based their positive recommendation partly on the fact that the manufacturer submitted clinical evidence that showed clear benefit (improved overall survival, progression free survival) in patients identified as BRAF V600 positive. If the manufacturer is unable to convince payers that the diagnostic adds tangible benefit to the use of the drug, payers are unlikely to recommend the drug and diagnostic combination.

If the access and funding requirements are different for the drug and the diagnostic this can lead to major challenges. For example, a drug could be approved for reimbursement without any funding available for the diagnostic. In these cases, if the manufacturer is unable or unwilling to support funding for the diagnostic, it will likely result in patients not being able to access the drug. Consequently, manufacturers should aim to understand the access and funding routes for both the drug and the diagnostic.

As well as the clinical benefit, it is also essential for payers to assess the economic impact of precision medicines, as there will likely be an increased healthcare cost burden of funding both the drug and the diagnostic. Alongside the cost of the diagnostic itself, payers will have to evaluate the associated healthcare resource impact (e.g. cost of administrating and processing the results of the diagnostic), especially if the patient population is potentially large.

Therefore, it is important to consider whether a precision medicine approach addresses a true unmet need or is only a marginal improvement on the current treatment paradigm. A therapy area where there is a tight balance between incremental benefit and financial impact is in the field of oncology. Oncology is the most prevalent area of precision medicine, as there can be clear disease biomarkers, the drug costs are very high, and patients have limited time to try multiple treatments. There are several examples where the incremental clinical benefit of precision medicine can be demonstrated but is not seen to outweigh the expected financial impact of funding these innovative therapies.

Whilst uptake is currently mixed, precision medicine is an area of significant investment by national governments

The final market access consideration is that each country has varying receptiveness for the uptake of precision medicines, which can affect both the likelihood of reimbursement and the speed to which the precision medicine can be brought to market. In the UK, where receptivity to precision medicine is high, the companion diagnostic and targeted therapy are jointly assessed by NICE in a formalised Single Technology Appraisal. In some markets (e.g. Germany), there is no official pricing and reimbursement process for precision medicines, resulting in the separate assessment of drug and diagnostic and significant delay. As a result, manufacturers may see an advantage in prioritising the receptive markets first in their global pricing and reimbursement strategy.

Whilst the current uptake of precision medicine is mixed, there is no doubt that this is an area that governments are willing to invest in. Several schemes have been launched globally over the last few years, from the United States’ $275m launch of the ‘Precision Medicine Initiative’ to China’s $9bn investment into precision medicine research as part of a five-year plan. In Europe, France, Germany and the UK have all invested significant funds into similar research projects, reflecting the growing desire to integrate precision medicine into mainstream healthcare provision.  It is likely that as payers become more familiar with the funding of such medicines, the pricing and reimbursement processes become more streamlined and less complicated for manufacturers.