The first JCA: exposing where the real work begins

Much of the reaction to the first JCA for tovorafenib has focused on what’s missing, namely limited comparative data and a relatively sparse PICO grid. But that risks missing the more important signal and there is a need to consider why this still represents an important process milestone. For many innovative therapies – particularly in rare or earlier-stage settings – this type of grid is what we should expect given the explicit nature of PICO definitions within the HTA process. The first report highlights challenges that are likely to become recurring themes, and therefore where companies need to plan differently for successful launch in Europe.

While it may have been striking to see only 2 out of 8 PICOs addressed, this reflects the reality of evidence generation for complex and rare diseases. Early approvals based on phase 2 or single-arm trial data often do not allow for robust comparator analyses. With the inclusion of all non-oncologic orphan drugs into the JCA from 2028, these cases will potentially become more common. The implication is not simply whether the PICO framework needs refinement, but how companies need to prepare for a system where evidence may never fully populate the JCA grid within complex PICO scenarios.

It also raises questions around how national HTA bodies will use the outputs from the JCA report in their P&R decision-making. The JCA provides a single, homogenous evidence package but this now needs to be interpreted across very different national appraisal frameworks using heterogeneous assessment criteria. With limited clarity on which PICOs matter most to which countries, and with Member States retaining the ability to request further data, the burden on manufacturers has not disappeared. It has simply shifted.

At the same time, the publication of a European-level clinical assessment alongside EMA approval moves value risk earlier in the launch process. Evidence gaps and uncertainties are now explicitly documented and shared across markets from day one, shaping how a product is perceived before national submissions even begin. In some cases, the absence of broader comparative evidence may also concentrate attention on the small number of available comparisons, giving them greater influence in shaping early value perceptions than their underlying data might warrant.  For companies, the first JCA report raises important strategic questions around the need to plan earlier, the trade-offs of early submission, and how to manage the uncertainty narrative in the context of the product’s broader value.

Ultimately, the sparse PICO grid is not something that can be avoided in some cases, it is something to be managed by the manufacturer. In the absence of clear comparative conclusions, companies will need to rely more heavily on country-level strategies, shaping comparator relevance, developing real-world evidence plans, and building coherent treatment narratives.

The JCA provides a common evidence base but not a common decision. The real test will be how national HTA bodies interpret this uncertainty and how effectively companies navigate it. How this is addressed over the next year for tovorafenib could provide key insights into the preparation required for future assessments. Will this be a case of reframing the narrative around the missing PICOs or a race to fill evidence gaps ahead of country level submissions?

Article by Nick Stringfellow

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