Access for rare disease treatments

Access for rare disease treatments


The S2 Hurdle: How the current funding pathway is restricting cross-border access for rare disease treatments

Innovative therapies for rare diseases may only be available in a select number of countries in Europe. However, the cross-border funding pathway currently in place to facilitate cross-border treatment of rare diseases (the S2 pathway) severely limits the ability of patients to access these cutting-edge treatments, exaggerating the disparity in access faced by patients.

This article will provide an overview of the S2 funding pathway for rare diseases, and how this obstructive access landscape has created problems for both patients and manufacturers across the continent

The S2 pathway

There are many scenarios in which a patient may require treatment in a different country to the one they live in. The main driving factor is typically that the treatment is not available in the home country (or will not be available in a justifiable time period). Additionally, the lack of specialist treatment facilities and expertise in the ‘home’ country forces patients to seek treatment elsewhere.

There are two funding routes available for the funding of European cross-border healthcare: the ‘Directive on Patients’ Rights in Cross-Border Healthcare’ (known as Directive funding) and the ‘Regulation on the Coordination of Social Security Systems’ (known as S2 funding).

There is an important difference which differentiates the two pathways. For the Directive, patients are required to pay costs upfront, and then later be reimbursed by their own healthcare authority. However, for the S2 funding pathway, a pre-approved form is used to guarantee payment between the health systems of the ‘home’ country and the ‘treating’ country. With the cost of treatments for rare diseases typically extremely high, the S2 funding pathway is the only pathway available for patients in desperate need of treatment not currently available in their home country. These typically include ATMPs and other gene therapies.

There are several criteria that must be met for the patient to be able to pursue S2 funding:

  • Must be able to provide clinicians statement (from EEA or Switzerland) as to the treatment needed and why
  • Requested treatment must be available under the home country’s health system, but cannot be provided within a medically justifiable time period
  • Requested treatment is not experimental or part of a drug trial

The second criteria point has significant implications for market access, as it suggests the products should theoretically go through national HTA and/or pricing/reimbursement decisions before funding is authorised. However, these decisions often only take place if the product is available within the home country, creating an interesting conflict at the core of S2 funding decisions.

Not fit for purpose

The S2 funding pathway has come in for strong criticism from both patient organisations and manufacturers.

A recent European Commission consultation on the Directive was hijacked by comments on the poor structuring of the S2 funding pathway, and the unsuitability for the funding of rare disease treatments. Common criticisms include the difficulty in implementing innovative cross-border access agreements (e.g. additional evidence generation or payment terms), which are typically required for gene therapies (high level of uncertainty), and the opacity in whether a treatment not reimbursed in the home country can be funded abroad. Additionally, administrative obstacles are recognised as being prohibitive, especially for rare diseases where the need for treatment is urgent. In some cases, approval for S2 funding can take months.

One of the companies to register their discontent at the S2 funding pathway was bluebird bio. Bluebird bio recently announced a cessation of European operations, just weeks after gaining European approval for elivaldogene autotemcel (a gene therapy for cerebral adrenoleukodystrophy). While the withdrawal was likely due to the wider difficulty in achieving European-wide market access, having a restrictive cross-border funding environment may lead to more manufacturers choosing not to launch in Europe if there is not an attractive commercial environment.

What next?

Unsurprisingly, there is widespread hope that the European Commission’s consultation on the Directive will lead to actionable change and better cross-border funding for rare disease treatments.

Commonly suggested improvements to the cross-border funding pathways include the removal of the requirement for upfront payment, as well as a greater reliance on pan-European HTA reviews to provide confidence to national health authorities that the treatments being funded in other countries are value for money.

The consequences of having an inadequate funding system impacts both patients and manufacturers. From the patient’s perspective, being denied the opportunity to access rare disease treatment that is available in neighbouring countries is very unfair and against the principles of the European idea.

For the manufacturer, an obstructive and overly bureaucratic system limits uptake and overall commercial success of the product, damaging the prospect of developing future treatments for rare diseases. Any manufacturer launching a rare disease product should monitor any upcoming changes to the European cross-border funding routes. While devising a European launch strategy, a manufacturer will have to carefully consider the balance of cost in establishing treatment centres in different countries against the uncertainty in relying on S2 funding.


  1. NHS: The S2 funding route   
  2. Cross-border healthcare – evaluation of patients’ rights  

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