Introduction to orphan medicines
EU orphan drug legislation (Regulation (EC) No 141/2000 and No 847/2000) was established following recognition that patients with rare diseases deserve the same quality of treatment as other patients with more common diseases. The regulation aimed to facilitate and incentivise the development of medicines outside normal market conditions to address unmet medical need for rare diseases. A medicine is considered an orphan drug if it is used for the diagnosis, prevention, or treatment of a life-threatening or chronically debilitating condition that is rare (affecting not more than five in 10,000 people in the EU) or where the medicine is unlikely to generate sufficient profit to justify R&D costs. Additionally, there must be no satisfactory method of diagnosis, prevention, or treatment of the condition already authorised, or, if such a method exists, the medicine must present a significant benefit to those affected by the condition. The medical condition must be defined and subsets of a disease are not allowed, unless medically recognisable and the drug will not benefit other subsets.
EU Incentives for orphan designation
There are many incentives to industry for developing an orphan drug, including automatic access to the Centralised Procedure (single EU-wide Marketing Authorisation) as well as currently 10 years market exclusivity post-authorisation for similar medicines, with an additional 2 years of market protection for compliance with paediatric investigation plan. Please note, these exact periods are likely to change with the implementation of the new pharmaceutical regulation which is currently under negotiation between the concerned European entities (Council, Parliament and Commission). Reduced fee or free EMA protocol assistance (scientific advice) to support the development of the orphan drug can be sought, with no restriction to the number of times this can be requested. Fee reductions also apply for orphan drug Marketing Authorisation Applications, post-authorisation procedures, annual fees and inspections.
Medical plausibility
Orphan designation of a medicinal product is decided by the Committee of Orphan Medicinal Products (COMP) at the EMA. Application can only be made for a recognised medical condition with sufficient data available showing that the medicinal product will benefit those affected by the condition.
Significant benefit
During the orphan designation application process, data are required that demonstrate evidence of likely significant benefit to those affected by the condition over any available existing treatments. In such cases head-to-head clinical data showing an advantage over the standard of care for a particular condition would need to be generated. Clinical data are not always required should data be available from validated nonclinical models of the disease showing benefit over existing treatments. Significant benefit can be demonstrated following improved efficacy, improved safety or a major contribution to patient care e.g., improved administration route. It is important to note that more than one benefit may apply and evidence from each category may be used to construct a robust argument for likely significant benefit. Biological medicines present an interesting case as the mechanism of action allows for precision medicines, where agents target particular biomarkers that not everyone with a particular condition will have. Where the new biological entity targets a different biomarker or a different genetically defined subgroup to available treatments, significant benefit may be demonstrated due to the benefit to a broader patient population within the condition compared to the population that can be treated by the authorised drug product.
Orphan designation at Marketing Authorisation Application
Orphan designation can be achieved very early in development but must be reviewed by COMP at the time of Marketing Authorisation Application in order to maintain the orphan designation post-approval. Often a marked period of time may have elapsed between orphan designation and Marketing Authorisation Application and there may be changes to the treatment options available for a condition, which would affect the assessment of significant benefit. Changes to the regulatory landscape may lead to different conditions for designation by COMP and orphan designation awarded previously may not be consistent with more recent COMP criteria. Compelling justification may be needed to defend the orphan designation at the time of Marketing Authorisation Application.
How can S-cubed help you?
S-cubed are able to support clients in obtaining and maintaining an Orphan Drug Designation from authoring of the scientific documentation, preparation and submission of the application through to responses to the EMA’s questions and determination of the outcome.
Any Questions?
If you have any questions on this topic, please don’t hesitate to ask. You can contact us here, via email, and telephone +44 1235 77 22 60.