The EU Joint Clinical Assessment (JCA) will extend to orphan medicines from January 2028, drawing rare disease therapies into a single, EU-wide clinical assessment. For developers of orphan products — where evidence is often built on small, single-arm studies — the JCA raises the bar on how clinical value is demonstrated. Preparing now is not premature; it is essential.
When rare disease therapies fall under JCA
Regulation (EU) 2021/2282 phases the JCA in by product type:
- From 12 January 2025: new active substances for cancer, and all advanced therapy medicinal products (ATMPs).
- From 13 January 2028: orphan medicinal products.
- From 2030: all remaining new medicines.
An important nuance is easily missed: a rare disease therapy that is also an ATMP — such as a gene therapy — or an oncology product is already in scope today. It does not wait until 2028. Every developer should map their product against the earliest applicable trigger rather than assuming the orphan date applies.
Why JCA is harder for orphan products
The JCA is a comparative clinical assessment, and rare disease evidence rarely fits that mould neatly:
- Small populations mean single-arm trials, surrogate endpoints and immature long-term data.
- National perspectives are consolidated into multiple PICOs (Population, Intervention, Comparator, Outcomes); comparators and standards of care differ across member states, so one pivotal trial seldom answers every PICO.
- Indirect treatment comparisons are frequently required where no head-to-head data exist.
- The final scope is confirmed only a matter of weeks before the dossier deadline, leaving little time to generate missing analyses.
Illustrative case study: an enzyme therapy for an ultra-rare disorder
The following is a hypothetical scenario for illustration only. A company develops an enzyme replacement therapy for an ultra-rare metabolic disorder. Its pivotal evidence is a single-arm study compared against a natural-history dataset, with a biomarker as the primary endpoint. During scoping, participating countries request different comparators — best supportive care in some, an off-label option in others — and ask for hard clinical outcomes rather than the biomarker. The consolidated scope therefore contains several PICOs. Because the company had prepared indirect comparisons and a robust natural-history comparator in advance, it was able to populate most PICOs within the assessment window and flag the remaining outcome gap transparently, rather than discovering it too late to respond.
How to prepare
- Anticipate the likely PICOs early, using national HTA precedent across the major markets.
- Invest in comparator and natural-history data before the scope is fixed.
- Consider a Joint Scientific Consultation to align the evidence plan with HTA bodies and the EMA in parallel.
- Synchronise the JCA dossier with the EMA marketing-authorisation timeline.
How PQRA helps
PQRA helps orphan-medicine developers get ready for the JCA — anticipating PICOs, strengthening comparator and natural-history evidence, preparing indirect comparisons, and coordinating Joint Scientific Consultation and dossier timelines with national reimbursement strategy in Greece and across the EU. We turn the 2028 deadline from a risk into a planning advantage.
Contact PQRA to prepare your rare disease therapy for Joint Clinical Assessment.
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