What role does real-world evidence (RWE) play in market access for rare disease therapies?

When working in rare diseases, clinical trial design is focused on an exceedingly small population. The clinical evidence in these cases often is based on open label, single arm studies that have a high degree of uncertainty due to the lack of randomization and direct comparison. The resulting data might fail to satisfy payers during price and reimbursement negotiations due to uncertainty about the treatment effectiveness. This is when RWE can make a major impact by:

• illustrating the disease burden and the natural history of an unfamiliar rare disease for payers.
• demonstrating the value your treatment adds compared to existing treatments (if any).
• defining the target population and clarifying expectations on the market size.
• acting as an external control arm to provide context for payers, particularly useful with ultra rare diseases where you cannot perform a direct comparative study.
• mitigating uncertainty about budget impact by proving treatment effectiveness.

How should companies approach the development of an RWE strategy?

Base your strategy on understanding your patient population and their needs. Then identify what endpoints and outcomes you expect from the pivotal clinical trial. From there, identify potential gaps and what evidence you will need to mitigate them. Once you know what RWE you need, you can determine how you will obtain or generate it. You can pull it all together in an integrated evidence plan in which you balance all available (or planned) evidence and all the identified needs from the medical, clinical, market access, commercial, and patient points of view, highlight the evidence gaps, and develop a cross-functional plan to address the needs and gaps.

RWE will become a pillar of your overall market access strategy. It can help define your target population and their needs and help with not only price and reimbursement negotiations, but also your commercial strategy. You can use real-world data (RWD) with prospective data collection to maintain the value of the treatment post-launch, especially in case of renegotiation.

How can companies identify the available data sources for targeted rare diseases?

A good way to identify the right data source for a targeted rare disease is to perform a RWD source mapping exercise by searching the existing literature (manuscripts and grey literature) to find all available RWD sources in a given geography, such as existing registries or population-based data sources. Combining secondary research with RWD source surveys or interviews, you gain insight into the data captured in the available sources and how well these sources may fit your needs.

Frequently, companies need to invest in creating a patient registry to ensure that adequate data is captured with sufficient quality in a timely manner. Designing the registry in collaboration with the regulatory agencies, health technology assessment (HTA) bodies, and patients increases the likelihood that the data will inform regulatory and HTA decision-making. It is important to keep in mind that this process is lengthy, driving the relevance of the integrated evidence plan and the need to start early.

How does RWE help estimate the size of the target rare disease population?

When the available literature is insufficient to determine the epidemiology (prevalence and incidence) of a target population, you can answer this question with a RWD study. Typically, you select a population-based data source to ensure that the epidemiological estimates are representative of the overall population. However, in rare diseases, challenges include the lack of specific ICD-10 codes to identify patients with the disease. To mitigate this challenge, you can develop an algorithm together with key opinion leaders (KOLs), such as physicians actively treating these patients, combining different characteristics (e.g., a combination of diagnoses codes with treatments or procedures) to identify the target population.

How can RWE provide additional insights post-launch?

Often, the European Medicines Agency (EMA) and/or HTAs will request a post-marketing commitment to submit follow-up RWD within a certain time frame. The EMA may require a post-authorization safety study or post-authorization efficacy study, whereas HTAs may ask for specific RWE studies to address their concerns. As with pre-launch, the post-launch phase relies heavily on RWE. Note that European payers prefer European data, so even if you have collected data in the US, you will want to use your EU-based patient registry to generate the required RWE.

What are three key takeaways regarding the usage of RWE market access for rare disease treatments?

Develop an integrated evidence plan that accounts for key stakeholders’ needs, including patients and healthcare providers, and considers your medical, regulatory, market access, and commercial needs and goals to identify your evidence gaps and define a strategy to address them.

Start the process of gathering RWE as soon as possible, at least three years before your expected access, pricing, and reimbursement negotiations will begin. A patient registry creation requires collaboration with KOLs and patients, which can take a year or more to set up, and then you’ll need time to collect sufficient data and analyze it.

Bear in mind that you will not find one data source that provides all the data you need. You will almost certainly need to build your own. Your goal is to identify the payer’s evidence requirements and reduce their uncertainty about treatment’s value. If your data is not sufficient, you can negotiate with payers and continue to generate and submit evidence that strengthens your position.

The bottom line is that in rare disease treatments, up-to-date and relevant RWE is fundamental to successful market access.