Written by Johann Sanseau, Associate Consultant: [email protected]
Haute Autorité de Santé (HAS) recently granted post-Marketing Authorisation (MA) early access (accès précoce) to Ojemda™ (tovorafenib) for relapsed or refractory paediatric low-grade glioma.
Under France’s two-step process for accès précoce, the Commission de la Transparence (CT) issues a scientific opinion and HAS’ collège takes the final decision. In this case, the collège reached a different conclusion from the CT’s opinion, which makes for an interesting case study as to how the two bodies evaluate the same evidence.
A post-MA accès précoce autorisation requires four eligibility criteria set out under Article L5121-12 of the French Public Health Code:
- Serious, rare or debilitating disease
- Lack of appropriate treatment
- Impossibility to defer treatment initiation
- Presumptively innovative nature, particularly compared to any clinically relevant comparator
The CT accepted criterion 1, but rejected criteria 2, 3 and 4. It considered off-label chemotherapy and trametinib to be appropriate existing options, and concluded that the pivotal single-arm Phase II study (FIREFLY-1) did not support a presumption of innovation. Its concerns under criterion 4 included a response-rate primary endpoint of limited relevance, absence of a robust comparator, exploratory QoL data, and growth retardation the CT flagged as particularly problematic in peri-pubertal children. Importantly, the CT also judged the development plan to be inadequate, noting that the confirmatory trial, FIREFLY-2, tests Ojemda™ against standard chemotherapy in first-line treatment, whereas the indication under review is for patients who have progressed after at least one systemic therapy (i.e., second-line).
The collège reached a different conclusion on each point. It held that off-label options supported by weak evidence do not constitute an appropriate alternative; a serious disabling disease without an approved treatment cannot have its treatment deferred; and it deemed the development plan adequate precisely because FIREFLY-2 exists, with confirmatory data due in 2028, despite this trial sitting in a different line of therapy to that which is under review.
Key takeaways
- Off-label use is not automatically disqualifying, but it is not automatically an appropriate alternative either. HAS’ doctrine treats a well-supported off-label option as appropriate by default; this decision shows that default can be overturned when the underlying evidence for that option is weak and unmet need is high. The default still favours treating a recommended off-label option as appropriate, so the burden sits with the applicant to show its evidence base is thin
- Disease severity and absence of approved options can change how the same evidence is read against the innovation criterion based on the data package, particularly in paediatric oncology and rare disease
- The two bodies didn’t just weigh the same facts differently, they fundamentally disagreed on whether a confirmatory trial run in a different line of therapy can count as confirmatory at all. For any programme where the confirmatory trial doesn’t match the exact population under review, this may suggest a strong unmet need case can still carry the development plan at the early access stage in France. However, the CT is likely to maintain these issues at reimbursement, so it is important to build the justification for why the mismatch does not undermine the relevance of the data
- This early access authorisation lasts for 12 months, with the collège requesting for updated compassionate-use data from the SACHA registry at the time of renewal. It is worth noting that the registry data is methodologically weaker than FIREFLY-1, with stable disease in 63% of patients and partial response in 24% of patients, and no prespecified response criterion or central reading of tumour response
- Ojemda™ was the first medicine to complete a Joint Clinical Assessment (JCA) under the EU HTA Regulation, a report which the HTA Coordination Group (which included HAS) endorsed by consensus. The JCA relied on the same FIREFLY-1 data, and with the JCA report taken into account by the CT in its forthcoming ASMR/SMR assessment, this likely reinforces rather than resolves its original concerns about the robustness of the evidence
Partners4Access will continue to monitor developments in the French PRMA landscape to ensure we can best support our clients with their product launches.
Sources:
- https://www.has-sante.fr/upload/docs/application/pdf/2026-07/dir10/ojemda_decision_et_avisct_ct-ap583.pdf
- https://www.french-business-law.com/french-legislation-art/article-l5121-12-of-the-french-public-health-code
- https://www.has-sante.fr/jcms/r_1500918/fr/acces-precoce-a-un-medicament
- https://health.ec.europa.eu/document/download/395c2ba0-849a-4f3b-9251-aa2495b3efd7_en?filename=hta_jca_mp_202406_tovorafenib_report_en.pdf
