Natalie Shalet, Founder and Lead Consultant at NAS Healthcare Solutions, shared a post on LinkedIn:
“The first JCA to complete under the EU HTA Regulation is sending a clear signal to market access teams: rare disease promise is not enough. Comparative credibility is key.
OJEMDA (tovorafenib) is a once-weekly oral RAF kinase inhibitor for paediatric low-grade glioma harbouring a BRAF alteration after prior systemic therapy. The unmet need is significant, these tumours cause neurological, visual, cognitive and endocrine harm, and there is no established European standard of care after prior treatment.
This was the first JCA to complete under the new framework. From it we can learn what level of scrutiny sponsors should expect. The assessment looks beyond single-arm efficacy and asks whether the comparative story is truly decision-grade across countries and subpopulations.
- What the assessors criticised
The core criticism was the reliance on an unanchored matching-adjusted indirect comparison (MAIC) against Bouffet 2023, the study the assessors used to compare against tovorafenib because there was no direct head-to-head trial. This approach only works if all important prognostic variables are adjusted for and outcome definitions are aligned. The assessors said neither condition was fully met.
The main issues were not about whether tovorafenib works but whether the comparative evidence was strong enough. The assessors said the analysis may not have fully adjusted for important factors like tumour type, location, and prior treatment, which matters a lot in a small rare-disease dataset.
They also flagged that the two studies did not define ‘response’ in the same way, so the comparison was not entirely comparable
and could favour tovorafenib. In addition, the indirect comparison was fragile because the study populations did not overlap well, and the PFS and safety data were harder to interpret because key details were missing or not comparable.
In short, a promising asset, but the evidence package was not robust enough to remove uncertainty.
- Overall outcome
This does not read as a straightforward endorsement of broad comparative benefit. The assessment suggests the asset has activity and relevance, but the comparative evidence was not sufficiently robust to support strong claims across all requested PICOs.
- What market access teams should learn
Market access teams should treat this as a learning for JCA readiness:
- Build comparator evidence early, not late.
- Pre-specify and defend outcome definitions.
- Align response criteria across studies wherever possible.
- Generate data that are comparative, not only single-arm.
- Anticipate subgroup evidence needs by age, molecular subtype and prior line of therapy.
- Document missing-data handling, covariate selection and sensitivity analyses with complete transparency.
I’m Natalie Shalet, I help teams derisk their programmes and generate evidence to ensure success.”
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