The German Federal Joint Committee (G-BA) has recently published its benefit assessments for tarlatamab and lurbinectedin, the second and third medicinal products to have completed the European Joint Clinical Assessment (JCA) procedure. The corresponding AMNOG assessments were initiated on July 1, directly following the first JCA procedure for tovorafenib. The assessments offer important insights into the interaction between European and national HTA processes, illustrating how evidence assessed within the JCA framework is considered in Germany’s early benefit assessments. It should be noted that all three procedures conducted to date involve orphan drugs, meaning that additional benefit is considered proven upon approval. Consequently, the identification of the EU PICOs relevant to the German healthcare context was not considered mandatory.

Tarlatamab: Differences Between the JCA and German Benefit Assessment

Tarlatamab is approved 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.

A particularly interesting aspect is the difference in assessment perspectives between the European JCA and the German national evaluation. While the JCA considered seven PICO questions across four different patient populations, the German benefit assessment was based on a broader population corresponding to the approved indication. Accordingly, the complete pivotal Phase III DeLLphi-304 study was submitted as part of the German dossier and was taken into account in the assessment due to the drug’s orphan status.

DeLLphi-304 is a multicenter, randomized, open-label study comparing tarlatamab with standard of care treatment consisting of lurbinectedin, topotecan, or amrubicin, depending on local practice. The G-BA identified benefits particularly with regard to overall survival and selected safety outcomes. At the same time, disadvantages associated with the occurrence of cytokine release syndrome were observed.

Lurbinectedin: High Consistency Between JCA and AMNOG

Lurbinectedin, in combination with atezolizumab, is indicated for the maintenance treatment of adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide.

In contrast to tarlatamab, only a single PICO question was defined within the JCA process. The data submitted by the pharmaceutical company for the European assessment simultaneously formed the basis of the German dossier and, consequently, the national benefit assessment.

The assessment was based on the multicenter, open-label Phase III IMforte study, which evaluated lurbinectedin plus atezolizumab versus atezolizumab monotherapy as maintenance treatment.

According to the G-BA, the IMforte study did not demonstrate significant differences in mortality or morbidity outcomes. However, the hazard ratio for overall survival was close to statistical significance, with a confidence interval of 0.65 – 1.01 and a p-value of 0.06. As is commonly the case in German benefit assessments, the statistically significant progression-free survival (PFS) result was not formally considered sufficient for demonstrating additional benefit. Regarding safety, disadvantages were identified for the time to first severe adverse event and the time to first serious adverse event. However, interpretation of these findings should take into account the differing observation periods between the intervention and control arm, which were influenced by earlier treatment discontinuations and study withdrawals in the control group.

What Happens Next in the AMNOG Process?

Until 22 October, the respective pharmaceutical companies, medical societies, and other stakeholders may submit written statements on the published benefit assessments. The G-BA’s oral hearings are set to take place on 9 November.

From a market access perspective, both procedures remain highly relevant. They provide important insights into how the new European JCA assessments are incorporated into national benefit assessments and highlight potential challenges at the interface between European and German HTA evaluation frameworks.

Sources:
1. GBA – Netzenbewertung GBA Tarlatamab – German (Accessed October 2026) https://www.g-ba.de/downloads/92-975-10059/2026-10-01_Nutzenbewertung-GBA_Tarlatamab_D-1340.pdf

2. EMA – Imdyllyra EPAR – Product Information English (Accessed October 2026) https://www.ema.europa.eu/en/documents/product-information/imdylltra-epar-product-information_en.pdf

3. Tarlatamab Summary Report – English (Access October 2026) https://health.ec.europa.eu/document/download/3d128877-e497-42e8-99e4-7a29f1f73061_en?filename=hta_jca_mp_202417_tarlatamab_summary-report_en.pdf

4. GBA – Nutzenbewertung – German (Accessed October 2026) https://www.g-ba.de/downloads/92-975-10045/2026-10-01_Nutzenbewertung-GBA_Lurbinectedin_D-1346.pdf

5. EMA – Zepzelca EPAR Product Information – English (Accessed October 2026) https://www.ema.europa.eu/en/documents/product-information/zepzelca-epar-product-information_en.pdf

6. Lurbectin Summary Report – English (Accessed October 2026) https://health.ec.europa.eu/document/download/8ebad6ee-a657-46cf-9fb1-2897c9abba88_en?filename=hta_jca_mp_202416_lurbinectedin_summary_report_en.pdf