On 5 November 2026 Germany's Federal Joint Committee (G-BA) closed the first AMNOG benefit assessment to include a joint clinical assessment (JCA) report under the EU HTA Regulation. The product was Ipsen's tovorafenib (Ojemda) for paediatric low-grade glioma, and the result was a non-quantifiable added benefit. The decision shows what a JCA report can and cannot do inside a national process, and it previews the problem orphan medicines will face when they enter JCA in 2028.
How Ojemda reached G-BA
The EU HTA Regulation has required a JCA for new centrally authorised oncology medicines and advanced therapies since January 2025. Orphan medicines follow from January 2028 and all centrally authorised medicines from January 2030. Tovorafenib was the first product through the process: it received a conditional EU marketing authorisation in April 2026, and the European Commission published its JCA report on 9 June 2026.
The licence covers patients aged 6 months and older with low-grade glioma carrying a BRAF fusion, rearrangement or V600 mutation, after at least 1 prior systemic therapy. Ojemda launched in Germany in May 2026, and the AMNOG procedure ran from 15 May to a decision on 5 November.
One PICO out of eight
The JCA scope, set by member states, asked for evidence on 8 PICO (population, intervention, comparator, outcome) questions across 3 populations. The pivotal FIREFLY-1 study is a non-randomised, single-arm phase II trial, so most of those questions had no comparative data.
- Comparative results existed for one PICO only. Ireland's NCPE (assessor) and IQWiG (co-assessor) found no comparative evidence for PICOs 1, 2, 3, 4, 6 and 8.
- The one comparison was weak. PICO 5 (children over 1 year with a BRAF V600E mutation) rested on an unanchored matching-adjusted indirect comparison with dabrafenib plus trametinib. The comparison covered about 17% of the licensed population and had an effective sample size of 5.81.
- The comparator gap was structural. Ipsen's own release on the report notes "the absence of a clearly established clinical comparator for much of the pLGG patient population".
What G-BA did with the report
Germany treated the JCA report as one input among several. G-BA still required a full national dossier, because country-specific requirements ruled out a complete waiver in favour of the EU submission. The German dossier carried its own epidemiology, statutory health insurance target population, annual treatment costs and an updated systematic literature review.
The evidence base also moved. The JCA used the two-year FIREFLY-1 data cut from May 2024; the German dossier used a three-year cut from June 2025, covering 137 patients across two cohorts. At that follow-up, Ipsen reports a median time to next treatment of 42.6 months.
The larger difference is legal. In Germany, an orphan medicine's added benefit counts as proven up to €30 million in annual sales, and G-BA decides only its extent. Sonja Optendrenk of G-BA made the point directly, noting that JCA reports carry no such privilege. IQWiG therefore assessed only patient numbers and costs, and G-BA judged the clinical evidence itself. With single-arm data and one weak indirect comparison, G-BA could not quantify the benefit.
What it means for market access teams
- The JCA adds work rather than replacing it. Budget for an EU dossier and a full national dossier on overlapping timelines, with data cuts that may differ between them.
- Plan for the PICO scope early. Member states will ask for comparators a single-arm programme cannot answer. A report with comparative results for only 1 of 8 PICOs is now public in every member state, including those with no orphan privilege.
- Orphan sponsors have until 2028. From January 2028 their EU dossiers face the same PICO scoping, and the JCA report will set out the comparative gaps that national orphan rules currently soften. Set natural history cohorts, external controls and comparator choices while trials are still being designed.
- The German rating rests on German law. The non-quantifiable outcome followed national orphan rules and the evidence available. Other HTA bodies will read the same JCA report through their own frameworks, so outcomes may diverge.
IQWiG's Beate Wieseler has said the JCA methods fit AMNOG principles, while the binding judgement on added benefit stays with member states. The vfa, Germany's research-based industry association, wants European-recognised endpoints to become binding nationally to cut duplicate work. For now, sponsors should plan on two assessments.
If you are planning a JCA submission or mapping likely PICOs for a single-arm programme, get in touch to discuss your evidence plan. Our HTA work is described on our services page.