Optimising Orphan Drug Development in the EU - DIA Europe 2019 update

EUDRAC exhibited at the annual DIA Europe Meeting in Vienna, Austria from 5th - 7th February 2019. A session was held on ‘Optimising Orphan Drug Development in the EU’ and below are some highlights of the discussions.

EU Figures

During the session a status of the EU ODD figures between 2000 and 2018 was provided. These figures can also be found on the EMA website.

Over time the majority of orphan designations was based on significant benefit (SB). Amongst the total number of EC designations obtained so far (2121), about 25% concerned new conditions (524). In 2018, 236 applications were submitted, 169 EC Designations were obtained and 92 withdrawals occurred after submission. Amongst the 164 initial orphan marketing authorisations and 22 extensions of indication granted to date, the majority (41%) was related to the Antineoplastic therapeutic area.

A recent article assessing the orphan condition definition challenges and evolution was introduced (‘Defining orphan conditions in the context of the European orphan regulation: challenges and evolution’.

Importance of Significant Benefit (SB) was discussed and it was acknowledged that it was more and more challenging to argue for SB in orphan conditions (difficult to generate incremental innovation in rare diseases). An article analysing 15 years of experience in Europe on demonstrating SB of orphan medicines was shared.

Challenges and opportunities: an Industry view

Some main challenges on orphan drug development as reported by industry representative were presented:

Significant Benefit: more and more challenging

  • Patient-relevant outcomes: how to best generate patient relevant outcomes to support SB
  • Innovative/complex designs: how to ensure that a single development plan is acceptable for all the stakeholders (choice of comparator, endpoint, statistical analysis…)
  • Balance regulatory and access with evidence generation: regulatory knowledge very dynamic in the post-approval setting. How to manage expectations of all stakeholders?
  • Regulatory decision-making with “RWE” evidence sources: registry data and natural history of the disease – what is their place in regulation?

Opportunities for orphan drug development were also discussed:

  • Evidence generation in the lifecycle: richness of data sources and technology that allow for more systematic evidence collection and understanding of natural history
  • Patient-centric drug development (and evaluation): patients at the center of R&D, steering development needs
  • Cross-stakeholder collaboration: clear understanding of the unmet medical need in rare diseases and efforts to collaborate (e.g. rare disease clusters, expedited pathways like PRIME, HTA EMA scientific advice)

Stakeholders collaboration during the development and registration of orphan medicines:

Collaboration between the stakeholders should be considered more and more as it is key to a successful development in a rare disease. Discussions between Developers and patient associations should be engaged regarding the right patient reporting outcomes as these tools are more and more used in clinical studies. Regulatory and HTA assessments have different remits but there is a need for more cooperation. Clinical representatives and HTA players should work together to define endpoints relevant to patients and HTA experts should be more open to the use of surrogate markers. The definition of an endpoint and appropriate statistical method should be discussed with regulators and statisticians and should be validated during scientific advise meeting at the EMA on a case by case.

Liaison FDA/EMA

Because rare diseases are a global issue, the Agency works closely with its international partners on the designation and assessment of orphan medicines, in particular the United States Food and Drug Administration (FDA), sharing information on orphan medicines under their confidentiality arrangement. The two authorities have also developed common procedures for applying for orphan designation and for submitting annual reports on the status of development of designated orphan medicines.

EMA and the FDA interact and collaborate regularly in the 'clusters' for 'Orphan medicinal products' and 'Rare diseases'.

A new collaboration between the EMA and the FDA is now in place to improve the sharing of information on various aspects of the development and scientific evaluation of medicines for rare diseases. This new working group on rare disease meets monthly via teleconferences. The existing FDA/EMA cluster on orphan medicinal products continues to meet quarterly to focus on information sharing and collaboration on orphan designation and exclusivity, as well as the agencies’ mechanisms to encourage the development of medicines for rare diseases.

More Information

For more information, please contact one of the EUDRAC offices.