Since January 2025, new innovative drugs have been subject to the European Health Technology Assessment (EU HTA). Initially, the procedure will only apply to ATMPs (gene and cell therapies) and oncology drugs. From 2028, orphan drugs will follow, and finally, from 2030, all new active substances will have to go through the EU HTA procedure. The interesting aspect is that only the clinical effects are assessed at the European level, while the assessment of added benefit and the path to reimbursement and price negotiation remain at the national level. But what are the special features for orphan drugs here? 

In January 2022, the EU HTA Regulation (EU) 2021/2282 (HTAR) came into force, creating the basis for the European benefit assessment. Based on this regulation, the more precise framework conditions for the process and criteria for the purely clinical evaluation of the study data should be developed in the coming years. The hope of the rare disease community was high, with the HTAR speaking of “methodologies which should be adapted to include specificities of new health technologies for which some data may not be readily available, such as, inter alia, orphan medicinal products, vaccines and ATMPs.” The so-called HTA Coordination Group, consisting of representatives of the respective national HTA authorities, shall also “consider the specificities of the health technology to which the joint work relates, including orphan medicinal products, vaccines and advanced therapy medicinal products.” 

However, these specific instructions from the HTAR to consider the challenges and limitations in the evidence generation of orphan drugs are not reflected in the now published methodological guidance documents. It merely states: “The provision of […] evidence in the dossier is based on international standards of evidence-based medicine […]. For some interventions, single-arm or non-randomised evidence may be the only evidence available. However, it may well be that this evidence […] is insufficient in the context of a JCA.” Orphan drugs are only considered when identifying relevant stakeholders, i.e. by considering Orphanet and European patient organisations. 

The question arises as to why this was not considered despite specific instructions. The problem lies in the principle of the EU HTA procedure itself, since decisions on added benefit and reimbursement amounts should remain at the national level. Special privileges or differing requirements at the European level do not appear appropriate in the JCA, since they would undermine purely national decision-making. Each country can decide for itself on special positions and privileges for orphan drugs; this is not called into question by the existence of a JCA report. However, whether an extremely negative JCA report, which can be expected due to the typically limited evidence for rare diseases, will or can eventually have a positive effect at the national level remains at least questionable. 

In addition, further interesting questions arise for Germany. For orphan drugs, the additional benefit is considered proven by the approval, i.e. proof of the additional benefit in relation to the appropriate comparative therapy formally does not have to be submitted. Since there is no such special orphan setting at the EU level, the pharmaceutical manufacturer must provide the required PICOs with supposedly different comparators in the JCA. This means that even if the pharmaceutical manufacturer does not wish to submit any or only certain data for the AMNOG benefit assessment, the JCA report may still contain public results for several PICOs with relevant comparators that could be used in the reimbursement negotiations.