Full Summary and Assessment of the Ojemda, Imdylltra, and Zepzelca JCAs

The first three Joint Clinical Assessment (JCA) reports have been published under the EU Health Technology Assessment Regulation (EU) 2021/2282 – the ‘ EU HTA Regulation’. These reports provide real-world insights into the new harmonised HTA process in Europe, including actual assessment scopes, submitted evidence types, and the Coordination Group on Health Technology Assessment’s (HTACG) approach to each type of comparative evidence and its contribution to relative clinical effectiveness assessment.

The JCA report for Ipsen’s Ojemda (tovorafenib) was published on the 9th of June 2026 and the JCA reports for Amgen’s Imdylltra (tarlatamab) and Jazz Pharmaceuticals’ Zepzelca (lurbinectedin) were published on 8th of July 2026. All three medicines are non-ATMP, orphan designated oncology products containing new active substances (NAS). Imdylltra and Zepzelca received centralised marketing authorisation in the EU based on comparative randomised controlled Phase III clinical trial data while Ojemda was granted conditional centralised marketing authorisation based on single-arm Phase II clinical data.

In this article we compare therapeutic indications, population-intervention-comparator-outcome (PICO) assessment scopes, outcomes, and discuss how these EU-wide relative clinical effectiveness assessments might impact market access in Europe.

The Health Technologies

Ojemda is available as a tablet and powder for oral suspension containing the active substance tovorafenib, a b-RAF serine-threonine kinase (BRAF) inhibitor. Ojemda is indicated as monotherapy for the treatment of patients 6 months of age and older with paediatric low-grade glioma (LGG) harbouring certain genetic mutations, who have progressed after one or more prior systemic therapies. The condition is a rare disease, with the incidence of BRAF-altered paediatric LGG (population aged 0 to 19 years) estimated by the developer at 0.33 per 100,000 persons in the EU. Although paediatric LGG generally has a favourable prognosis, with a 10-year overall survival of 85%-96%, it is chronically debilitating and associated with substantial long-term morbidity and functional impairment.

Imdylltra contains the active substance tarlatamab, a T-cell engager antibody that binds cancer cell proteins with T-cells. Imdylltra is administered by IV infusion and is indicated as monotherapy for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), who require systemic therapy following disease progression on or after first-line treatment with platinum-based chemotherapy. SCLC is also classed as a rare disease, affecting 1.4 in 10,000 persons in the EU. The condition is chronically debilitating and life threatening due to its rapid progression and the development of widespread metastases, with a poor 5-year overall survival.

Zepzelca contains the active substance lurbinectedin, an alkylating agent and oncogenic transcription inhibitor. Zepzelca is available as a powder concentrate for solution for infusion and, similarly to Imdylltra, it is indicated for the orphan condition ES-SCLC, but in combination with atezolizumab for the maintenance treatment of adult patients whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide.

The PICOs

The first three JCAs demonstrate three distinct assessment-scope models. Ojemda had the broadest scope, with eight PICOs across three paediatric LGG populations. Imdylltra also had a broad scope, with seven PICOs across four clinically distinct ES-SCLC populations. While Zepzelca had the narrowest scope, comprising a single population and one PICO aligned with maintenance treatment following first-line induction therapy.

Ojemda: Indirect Comparative Evidence Included for One out of Eight PICOs

Ojemda was assessed across three biomarker-defined paediatric LGG populations, generating eight PICOs with comparators including dabrafenib plus trametinib, vinblastine, carboplatin plus vincristine, TPCV, everolimus, bevacizumab plus chemotherapy, and trametinib. However, in the final JCA indirect comparative results were included only for PICO 5 (Ojemda versus dabrafenib plus trametinib in the BRAF V600E population). An unanchored Matching Adjusted Indirect Comparison (MAIC) was also submitted for PICO 7 but was not included due to insufficient information on the TRAM-01 study. The remaining PICOs lacked suitable comparative evidence.

Imdylltra: Seven out of Seven PICOs Addressed with Evidence of Varying Quality

Imdylltra was assessed in adults with ES-SCLC after progression on first-line platinum-based chemotherapy. The scope was divided into four populations based on platinum sensitivity and eligibility for platinum retreatment, resulting in seven PICOs. Comparators included topotecan, CAV, platinum retreatment, and platinum-etoposide regimens.

Zepzelca: A Single PICO Addressed with a Comparative Randomised Controlled Trial

Zepzelca’s assessment scope defined a single PICO comparing Zepzelca, in combination with atezolizumab, to atezolizumab monotherapy in the indicated patient population. This narrow scope aligned closely with Zepzelca’s registration Phase III trial resulting in a more straightforward and directly assessable JCA.

The Outcomes

Across all three JCAs, the requested outcomes were broadly similar, reflecting the EU HTA focus on patient-relevant relative clinical effectiveness and safety. Common domains included overall survival, progression-free survival, response rates, health-related quality of life, health status and safety outcomes.

Ojemda: Outcomes Requested Exceeded Available Evidence

The JCA requested comparative evidence on survival, progression, response, quality of life, symptoms, fatigue and safety outcomes. However, the pivotal study was a single-arm Phase II trial, and no connected evidence network could be established. As a result, only one unanchored MAIC was included for PICO 5, with most PICOs remaining unassessable. The JCA therefore provided only limited comparative results and highlighted significant evidence gaps despite regulatory approval.

Imdylltra: More Evidence, Variable Certainty

Imdylltra was assessed across a broad range of outcomes including survival, progression, response, quality of life, symptoms and safety. The evidence package combined direct comparative data, indirect treatment comparisons and network meta-analyses. While this allowed assessment of more PICOs than for Ojemda, outcome availability and certainty varied across populations and comparators. The JCA demonstrates that evidence quantity alone is insufficient; comparator alignment, endpoint availability and methodological robustness are equally important.

Zepzelca: Narrow, Well Addressed Assessment Scope

The JCA requested outcomes including survival, progression-free survival, response outcomes, quality of life, symptoms, health status, safety and immune-related adverse events. The Phase III pivotal trial provided direct comparative evidence for the single PICO, enabling assessment of most key outcomes. However, some endpoints were unavailable while analyses of immune-related adverse events and patient-reported adverse events assessed using the PRO-CTCAE framework (Common Terminology Criteria for Adverse Events) were excluded due to methodological limitations. Although Zepzelca’s pivotal trial data directly addressed the population and comparator assessment scope, uncertainty remained around response outcomes, patient-reported outcomes, safety and the durability of overall survival benefit.

The Impact

What the First Three JCAs Indicate for Future EU HTA Strategy

The first three JCAs provide insightful case studies into the EU’s new HTA framework. As intended, the JCA’s represent comparative assessments driven by the indications submitted to EMA, Member State comparator expectations and patient-relevant outcomes.

The comparison highlights that alignment between the target indication, likely PICOs, comparators, endpoints and evidence-generation strategy is critical for JCA readiness. The Ojemda report illustrates the challenges of broad multi-PICO assessments supported mainly by single-arm data. Imdylltra shows the complexity introduced by multiple populations and comparators. Zepzelca demonstrates how a narrow indication can result in a focused PICO assessment scope. The single PICO was well addressed by direct randomised evidence, while issues such as outcome maturity, risk of bias, external validity and safety interpretation remained present.

Implications for European Market Access

Although the JCA provides a common EU-level clinical assessment, value, pricing, and reimbursement decisions remain the responsibility of individual Member States. As a result, uncertainties identified within a JCA are likely to influence national HTA appraisals and payer negotiations.

For products with limited comparator evidence, such as Ojemda, uncertainty may increase the importance of additional evidence generation or managed access approaches. For products with multiple PICOs, such as Imdylltra, value propositions may need to be tailored to different subgroups and national contexts. Even for products with direct evidence and a focused PICO, such as Zepzelca, national bodies are likely to scrutinise survival maturity, patient-reported outcomes, trial representativeness and safety trade-offs.

Practical Lessons for Developers

Developers should assess likely JCA PICOs early in development, ideally before pivotal trial design is finalised. This includes identifying expected comparators, relevant subgroups, representative patient populations and appropriate patient-relevant outcomes.

Direct comparative evidence is likely to provide the strongest basis for JCA. Where indirect comparisons are necessary, planning should address evidence-synthesis requirements, endpoint comparability, covariate availability and sensitivity analyses. Attention should also be paid to data maturity, risk of bias, patient-reported outcomes and safety analyses, as methodological weaknesses can limit the use of evidence within a JCA.

Overall, the first three JCAs reinforce a clear message: successful EU HTA submissions require integrated regulatory, clinical and HTA evidence planning from early development rather than retrospective adaptation of the regulatory dossier.

DLRC Supports JCA Readiness and Evidence Strategy

DLRC translates JCA findings into forward-looking development and access decisions, covering PICO and label strategy, evidence planning, scientific advice, dossier quality assurance and national HTA risk mitigation.

Contact us today at hello@dlrcgroup.com to discuss how DLRC’s award-winning consultants can help support organisation in navigating JCA requirements and maximising the value of your evidence-generation strategy.