On 16 June 2022, the G-BA published its findings on the benefit assessments of Gavreto (pralsetinib) and Abecma (idecabtagen vicleucel). Both drugs are quite promising oncology treatments, but the G-BA was only able to conduct a limited benefit assessment due to methodological and/or quality flaws in the submitted data.
Pralsetinib
Pralsetinib is indicated as monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor. It is the only available therapy in this indication.
For the assessment, the G-BA identified five subgroups differentiating among adults with RET fusion-positive advanced NSCLC
- with a PD-L1 expression of ≥ 50% of the tumour cells,
- with a PD-L1 expression of < 50% of the tumour cells,
- after first-line therapy with a PD-1 / PD-L1 antibody as monotherapy,
- after first-line therapy with cytotoxic chemotherapy, or
- after first-line therapy with a combination of or sequential treatment with a PD-1/PD-L1 antibody and platinum-based chemotherapy.
In each of these groups, the ACTs were either a PD-1/ PD-L1 antibody – pembrolizumab, atezolizumab or nivolumab, as monotherapy or in combination with platinum-based chemotherapies – chemotherapies, or therapies including a tyrosine kinase inhibitor.
However, the manufacturer submitted only data from a non-controlled study and an indirect treatment comparison (ITC) for the endpoints OS and PFS. The non-controlled trial design makes it impossible to assess the additional benefit over an ACT.
Therefore, the G-BA concluded that the data provided was not appropriate to assess the additional benefit.
Overall, the G-BA assigned “Additional benefit not proven” to all five subgroups.
The G-BA restricted their resolution until 31 Dec 2027 for subgroups 1 and 2. By that time, data from the additional study AcceleRET-Lung should become available.
The G-BA emphasised that despite the negative finding, pralsetinib may still represent a suitable treatment option in specific cases.
Idecabtagen vicleucel
Idecabtagen vicleucel is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti CD38 antibody and have demonstrated disease progression on the last therapy.
The CAR-T cell therapy is an orphan drug with annual treatment costs of €350,000. Its additional benefit is deemed proven.
The manufacturer submitted data from the single-arm registrational KarMMA trial, the supportive single-arm study CRB-401, as well as several ITCs based on other studies.
While the G-BA can use ITCs to assess the additional benefit, albeit with lower certainty, here this was not possible. The manufacturer carefully explained the methodology of the ITCs, but did not consider all relevant confounders. Therefore, it remained unknown if the included study populations were sufficiently comparable.
Overall, the G-BA was unable to use the ITCs, and saw a hint of not-quantifiable additional benefit.
Further reading related to benefit assessments in Germany
- Which endpoints are important to the G-BA and IQWiG?
- How does the G-BA pick the appropriate comparator?
- When can an off-label drug be the appropriate comparator therapy?
- Regular and abbreviated early benefit assessments – Is this the end of orphan drug privileges?
- HTA guide
- EUnetHTA21 starts preparation for joint HTA from 2024
- G-BA assessment of orphan drug gene therapies, Zolgensma and Libmeldy
- Why did the G-BA assess Trimbow now?
- IQWiG methods version 6.0, English
- The biggest SHI fund, the AOK, proposes an end to free pricing in Germany
- New government coalition plans AMNOG, pricing and other reforms
- Prof. Dr. Karl Lauterbach is the new German health minister
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