Insights from the World Orphan Drug Congress

Navigating Change: Insights on EU Orphan Drug Legislation, Challenges, and Patient Access

Clinigen’s Working Group, 'Changes in orphan drug legislation and patient access', held at this year’s World Orphan Drug Congress, discussed the current EU legislation pertaining to orphan medicines, what's worked well, and how the changes will affect stakeholders and patient access. The room was extremely well attended, with people from industry, patient advocacy groups, carers, and Regulatory Agencies in attendance.

Orphan drug designations, brought about in 2000, provides incentives for research and development into orphan drugs to meet the needs of rare disease patients. Incentives include tax credits for qualified clinical trials, exemption or reduction of regulatory fees, research grants, protocol assistance, 10 years of market exclusivity after approval (+ an additional 2 years if a PIP is granted at time of review) and Central Authorisation across the EU via a single application.

The consensus in our Working Group was that this had been somewhat successful. According to EFPIA, the number of EU-approved medicines for rare diseases was in single digits 2 decades ago, and to date over 205 new treatments for orphan diseases have been approved. But there is a long way to go given there are over 6000 recognised rare diseases according to EMA (Orphan designation: Overview | European Medicines Agency (EMA)) and it is alleged that up to 95% of rare diseases still do not have an authorised treatment (Staying ahead: the case for a European Action Plan for Rare Diseases | Global Counsel).

The European Commission (EC) formally recognised this by publishing their executive summary and proposed changes to EU legislation which will repeal 726/2004 and 141/2000 on orphan medicines and the paediatric regulation 1901/2006. The EC’s executive summary states that “whilst there has been a lot of positives, there have been wide-ranging developments and discoveries in science and a globalisation of the pharmaceutical sector. These changes, which have focused attention on unmet medical needs, patient access, and the budgetary impacts of medicines, call for a review of policy intervention in the field of rare diseases and medicines for children”.

The evaluation identified the following problems:

• medical needs of children and patients with rare diseases that are not sufficiently met;
• the price of medicinal products poses a challenge for healthcare systems (affordability);
• patients have unequal access to medicines across the EU;
• the system does not accommodate innovation well enough and creates unnecessary burdens.

Some of the proposed changes include:

• Duration of market exclusivity to be modulated: “high unmet need” remains at 10 years, for “well-established use orphan products” will be 5 years, and all other orphan products will benefit from 9 years.
• Designation validity will go from no timeframe to limited to 7 years with an annual report to prove validity.
• Additional rare indications will only benefit from a further 12 months of market exclusivity, whereas previously it was a new designation per indication as per the “Global Orphan MA approach”.
• Criterion-based definitions of Unmet Medical Need (UMN) and High Unmet Medical Need (HUMN) to assist regulatory and HTA bodies in identifying genuinely innovative products. In the new legislation, orphan drugs will be considered to address a HUMN if:

1. There is no authorised medicine for the condition, or the new product brings exceptional therapeutic advancement; and
2. The new product results in a meaningful reduction in disease morbidity or mortality.

Thoughts expressed within our Working Group were that this new proposed legislation will hurt orphan drug development, and therefore rare disease patients, there is still a lack of definition of high unmet medical need, and there remains a lack of harmonisation across EU Member States, as well as globally. However, it could be argued that whilst these changes somewhat undermine the original incentives to innovators, these changes can also foster quicker market entry for generics and biosimilars, which would likely enable wider and more affordable patient access.

Another way for patients with no viable options to gain access to potentially life-saving medicinal products is unlicensed supply. Unlicensed supply mechanisms exist for patients with no treatment options approved on their market, who cannot be enrolled in a clinical trial, and who are suffering from a seriously debilitating, life-threatening, or chronic illness. Unlicensed mechanisms exist in a lot of countries around the world. According to Clinigen’s regulatory intelligence, there are around 93 countries that do not have solid frameworks for this kind of supply, but there are disparities and a lack of harmonisation across EU Member States, let alone the rest of the world. This does not enable equitable patient access, something that we spoke about in our Working Group.

We were delighted by the attendance at our Working Group, and want to thank everyone that joined us, for your insights and valuable contributions. Clinigen took some key takeaways from our Working Group, and the Congress as a whole. Patient voice is crucial and must be formally integrated into the research, development, and regulatory processes. Engagement across functions and policymakers is encouraged.

Truly equitable access for all patients is not happening at an EU MS level, let alone globally, and unlicensed supply is often an appropriate solution for some patients to gain access to innovative medicines but is not always a possibility for Sponsors.

Real-world data/evidence should be formally recognised in unlicensed supply legislation/guidelines and create harmonised approaches for collecting and using real-world data to encourage patient and carer perspectives to be taken into account across the lifecycle and could support quicker diagnosis, and better care and access for rare disease patients.

The Working Group at this year’s World Orphan Drug Congress highlighted the progress made under current EU orphan drug legislation, while also addressing critical gaps and challenges in patient access and drug development. Proposed changes to the legislation aim to address unmet medical needs, affordability, and innovation barriers but may inadvertently reduce incentives for orphan drug development. The discussions emphasised the importance of harmonisation across Member States, the role of unlicensed supply in bridging access gaps, and the need for integrating patient voices and real-world evidence into decision-making. Clinigen remains committed to fostering collaboration and driving solutions that improve access to innovative treatments for rare disease patients worldwide.

Contact us to learn more about current EU legislation pertaining to orphan medicines.