OBJECTIVES :

To identify strategies used in Orphan and gene therapy reimbursement to manage comparator issues

BACKGROUND

Often in rare diseases pivotal trials are carried out in small numbers, as single arm studies or with only placebo control. It is often cited that no licensed or common comparators exist. This provides considerable challenge for reimbursement. Given costs associated with Gene therapies this challenge is considerable.

METHODS

A Literature review was performed to identify and study the EU reimbursement of Orphan drug and gene therapies. Analysis was carried out to identify the trial characteristics, the nature of comparators utilised in assessments and the availability of treatment of disease versus symptom management.

RESULTS :

Since 2015, 132 Orphan drugs have received EU marketing authorisation, similarly 9 gene therapies have received EU marketing authorisation. In Orphan drug trials the median number of patients is 538, In gene therapy pivotal trials this ranges from 18-126 with a median of 75.

In Orphan drugs a control arm is usually (>80%) included in study design however in the pivotal trials of the gene therapies reviewed 66% were single arm studies and 33% had no control arm.

In review of Orphan and Gene therapy reimbursement, where comparative data is lacking, but single or multiple comparator treatment(s) exist, some form of data synthesis is required. Where no authorised treatment exists and unlicensed treatments are used, an average (weighted) distribution of comparators is utilised for economic analysis, often based upon clinician feedback. Where no treatment is available, natural history and cost of lifetime disease management is ordinarily utilised as for economic comparison.

CONCLUSIONS :

Given the paucity of comparative data in Orphan drug and gene therapy reimbursement it is important to synthesise the cost of disease management when no comparator exists, and where multiple unlicensed treatments exist an average cost can be utilised in economic evaluation.