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How to Leverage Real-World Evidence to Achieve Orphan Drug Designation

Globally, over 300 million people suffer from a rare disease. 7,000 rare diseases have been identified, and the list is growing: according to the 2021 European Expert Group on Orphan Drug Incentives Report, five new rare diseases are added each week, and 95% of rare diseases are currently without authorized treatment. In the EU, Orphanet tracks the list of rare diseases, where a rare disease is one that affects less than 5 in 10,000 people in Europe or less than 200,000 people in the US.

For diseases that are not well documented as rare, or for a new disease, a robust RWE study would be the most appropriate approach to estimate the epidemiology of a disease and indeed demonstrate if it is rare (prevalence of <5 in 10,000), critical to receive ODD."

Orphan Drug Designation: What It Is, Why It Matters, and How Can RWE Help?

An orphan drug is defined as a medicinal product (drug) used for the prevention, diagnosis, or treatment of a rare disease. Under the Orphan Drug Regulation in the EU, sponsors with a drug that targets a rare disease can apply for an Orphan Drug Designation (ODD). The ODD comes with meaningful incentives to encourage and support sponsors who are serving such a small population of patients.

Obtaining an ODD is challenging and may require sponsors to leverage real-world evidence (RWE). To receive the ODD, sponsors must meet the following eligibility criteria:

  • Disease/Condition prevalence: Less than 5 in 10,000 EU citizens in Europe or less than 200,000 people in the US. This data must be focused on Europe for the EU market.
  • Medical plausibility: Data (non-clinical and clinical if available) should support the rationale for using the drug in the disease. The sponsor should be concise, descriptive, and clear in how the data findings relate to the disease.
  • In the EU only, the sponsor must demonstrate a significant benefit by providing evidence (bibliographic or experimental, as applicable) supporting that no satisfactory methods of treatment exist, or if any such methods exist, the drug candidate must be of significant benefit to those affected by the condition.
  • Clinical superiority: Only applicable at the time of license application if a similar drug is approved for the same use.

For diseases that are not well documented as rare, or for a new disease, a robust RWE study would be the most appropriate approach to estimate the epidemiology of a disease and indeed demonstrate if it is rare (prevalence of <5 in 10,000), critical to receive ODD.

The benefits of receiving an ODD include:

  • 10 years of market exclusivity
  • Financial incentives including fee waivers and EU funding programs
  • Protocol assistance from EMA
  • Programs to expedite development and approval including accelerated assessment as well as priority medicines (PRIME)

Estimating a disease prevalence with RWE

Sponsors can review the EU list for the disease their drug is targeting. If the disease is there, they can apply for the ODD. If the targeted disease is not yet on the rare disease list, there will be a long journey for the company to first demonstrate if the disease is indeed rare and apply for ODD. Sponsors must characterize the epidemiology of the disease and assess if it meets the rare disease.

Start with a systematic literature review to understand if the natural history and epidemiology of the disease are already described with sufficient quality.

If literature does not exist or is insufficient, it’s time to develop a real-world evidence strategy!

Step 1: Characterize the patient’s journey

How do patients navigate the healthcare system until they reach a diagnosis (which can take years for rare diseases)? How is the disease managed? Engaging with patients or patient associations can be crucial if the natural history of the disease is not well documented. Input from clinical experts informing how they diagnose and manage patients is also key. The patient journey will inform the algorithm used in the RWE study to identify the target patient population.

How to

Engage Patients in Rare Disease Product Development

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Step 2: Leverage population-based national RWD sources

Leverage population-based national RWD sources to measure the epidemiology of the disease and estimate its prevalence. This can be challenging in rare diseases. One approach is to use a set of disease identifiers such as diagnoses, tests, procedures, and treatments that are somewhat unique to the target disease and use this to build a decision tree to identify the target patient population from the large population-based RWD sources.

Step 3: Leverage enriched data (chart reviews)

If the information above is not enough to identify the target patients, we collaborate with hospitals and physicians that are experts in the disease to examine anonymized patient data from electronic medical records and build an algorithm that can later be applied to the same population based RWD sources with a certain degree of specificity and sensitivity.

Step 4: perform advanced statistical analyses to estimate the prevalence and incidence of the disease

RWE is the best approach to obtain a representative measurement of the number of people suffering with the disease. The key is to robustly identify the target population. Collaboration with clinical experts is key to validate the algorithm used to identify the target patients as well as to interpret the results.

Step 5: ODD dossier submission

Based on the evidence generated on the targeted population and clarity of the condition/disease definition, a scientific advice or pre-submission meeting with the Committee for Orphan Medicinal Products (COMP) may be required before the ODD dossier submission. The purpose of such interaction with agency(ies) is to validate the approach and to secure the ODD.

Rare Disease and Orphan Drug Expertise

Alira Health works with sponsors all along the journey of rare disease drug development. Our patient engagement team can define the patient journey and the care pathway leading to the diagnosis of a rare disease. Our RWS team works with large national RWD sources to measure disease prevalence and has relationships with KOLs throughout Europe and the US. We have completed 16 ODD feasibility analyses, held seven pre-submission meetings with the COMP, and prepared and submitted 12 ODD dossiers to heath agencies in the EU and US.

We also have market access expertise in rare disease. After an ODD is granted, there are multiple fast track pathways for orphan drugs which offer sponsors different benefits in each country. We know how to optimize these pathways for sponsors to help patients access the product as soon as possible.

If you’re developing a drug targeting a rare disease, we can support you with the complexity of obtaining an ODD.

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