Three pitfalls you must avoid to succeed in the European rare disease ecosystem

Treating the EU as a single, homogeneous market

While the European Medicines Agency centrally evaluates orphan medicines for EU marketing authorization, Europe is made up of 27 countries, each with its own government, legal framework, and cultural specificities.

A common mistake, especially of non-European companies entering the European market, is applying the “one size fits all” strategy across the EU. For this reason, here we list some country-specific aspects that are fundamental to consider when approaching the European market:

• Language: it may sound obvious, but it is not. As of today, there are 24 official languages spoken in Europe, thus English is not always the best option to build relationships with local stakeholders. Some intangible barriers could be overcome only when speaking their native language. Furthermore, many administrative processes and institutional interactions must be conducted in the official language of the country.
• Diagnostic paths can vary within countries for a combination of structural and organizational factors. Each country has its own healthcare system (public, mixed, or private), with varying levels of access to specialists, diagnostic tests, and advanced technologies. This directly affects the speed and accuracy of diagnosis. Moreover, not all countries have the same number of expert centers for rare diseases or are equally connected to the European Reference Networks (ERN). Where such centers are scarce or difficult to access, the diagnostic pathway can be longer. Training and continuing education programs also vary between countries, influencing the ability to suspect and identify these conditions early. Lastly many rare diseases require genetic testing. However, access to advanced tests (such as genome sequencing) may differ due to costs, reimbursement policies, or availability in national laboratories.
• Early access programs: each country has its own early access programs, with different laws regulating them, different funds available and unique requirements to consider when applying. Understanding this and reaching out to someone with deep expertise in these programs in the country you are targeting is fundamental to increasing the chances of success when applying.
• Price negotiation and reimbursement processes are managed at the national level and can vary substantially from one country to another. For this reason, relying only on EU-level data is risky without digging into country peculiarities: when sitting at the table of price negotiation, national HTAs bodies greatly value robust and local data, which increase the credibility of the value story. Local data show a deep understanding of the healthcare environment, make health projections more realistic, and help tailor the access strategy to specific priorities and constraints.

Underestimate the European rare disease local network

Local clinicians, scientists, nurses, and patient associations are best positioned to understand the real-world problems patients are facing, the diagnostic issues of a specific country or region, or the difficulties in enrolling patients in clinical trials.

The key, therefore, is to engage people working directly in the field who can interact with the key players, involve them, understand their challenges, empathize with them, and build a network of stakeholders able to provide honest and trustworthy feedback essential to improving the outcome. This is why co-developing local education, care pathway materials, or early data initiatives ensures your solution is credible, relevant, and immediately useful as it is shaped by those who will deliver and experience care.

Very importantly, relying on a strong local network of KOLs is fundamental to avoid difficult negotiations, longer timelines, and weak adoption post-launch. This happens because in rare diseases, awareness does not automatically translate into adoption. What truly moves the needle is the local network, such as reference centers, early adopters, small but influential clinicians, patient advocates. Neglecting these small players, often outside the major academic centers, can slow down the process far more than expected.

For all these reasons, teams that are not immersed in the local healthcare and social system should be avoided. This is particularly important in all the pre-launch activities, that are primarily medical and are fundamental to build the solid network at the base of the mission success. In this regard, we have been partnering with a US company which initially planned to approach Europe with a single MSL expected to cover the Big 5. This is exactly what is critically important to avoid. One MSL cannot ensure thorough, on-the-ground coverage across multiple countries, nor is it realistic to expect a single individual to navigate the specific regulatory, clinical, and cultural nuances of each market.

To address this strategic gap, we proposed a different approach: a team of experienced professionals with a strong background in Medical Affairs, capable of operating effectively within their respective local contexts.

In less than six months, each team member successfully mapped and engaged with all key reference centers for the disease area of interest. They also helped raise disease awareness and increase understanding of the ongoing clinical study by actively participating in several national congresses.

This level of execution would not have been achievable by a single MSL within the same timeframe. The ability to operate in parallel across multiple countries, leverage established local relationships, and ensure consistent presence at key centers and national congresses was critical to accelerating both network development and disease awareness.

Delay real-world evidence generation

Real World Evidence (RWE) is becoming increasingly crucial for the different European HTA bodies because they rely more and more on it to evaluate the sustainability, long-term outcomes, and real-life effectiveness of the therapies. What truly makes the difference is effectiveness: the ability to demonstrate clinical impact in real-world settings. In addition, many European countries require pharmacoeconomic data when negotiating prices and reimbursement, and RWE can provide these crucial data during the post-authorization phase.

RWE is fundamental because it complements randomized clinical studies, especially for rare diseases where cohorts are often small.

Starting registries or observational studies too late can weaken the value story, complicate reimbursement negotiations, and create avoidable delays post-launch. Addressing these factors early on is crucial when building a successful strategy and team in Europe.

If you are planning to expand your business in the European rare disease market, let’s connect to explore how to navigate these complexities and unlock your full potential in this market.