Patient registries: EMA officials highlight orphan drug development opportunities

Regulatory news

| August 25, 2022 | By Ferdous Al-Faruque

European Medicines Agency (EMA) officials tout the benefits of patient registries to support regulatory decision-making for orphan drugs in a recent review article in Frontiers in pharmacology.

Citing the growing use of real-world evidence (RWE), including patient registries, officials say these sources offer “useful evidence at different stages of the orphan drug life cycle, including during the development phase. by providing information on the natural history of the disease, its prevalence and incidence to contextualize pre-authorization clinical studies, to support initial and maintenance applications for orphan designation by demonstrating significant benefit over existing treatments, but also to generate long-term post-authorisation data on their efficacy and safety profiles.

The article provides examples of registries that have been used in the evaluation of various orphan drugs, including several advanced therapy drugs (ITMs), and provides an overview of how these data sources have facilitated decision-making. agency decision. For example, they note that the Committee for Medicinal Products for Human Use (CHMP) has successfully used the Cystic Fibrosis Foundation patient registry to expand therapy to certain subpopulations of cystic fibrosis with a certain genetic marker.

They also note that the EMA has embarked on an ambitious project to mine RWE from a large number of registers through its Real-World Data Analysis and Query Network (DARWIN EU). Regulators hope the network will support regulatory decision-making by “establishing and maintaining a catalog of known and relevant data holders, continuously ensuring the discoverability and quality of data held by data holders in order to conduct studies and scientific analyzes on behalf of the European Union”. EMA Medicines Regulatory Network and Scientific Committees.

EMA’s Joint Big Data Steering Group recently published a third work plan which sets out a timeline for developing DARWIN EU. According to the plan, by the end of this year, the research database will launch four studies with the help of 10 research partners to collect real-world evidence (RWE). By the end of 2025, this is expected to grow exponentially, resulting in the collection of 100 studies with the help of 40 partners. (RELATED: EMA, HMA describe the evolution of the DARWIN EU real-world database, Regulatory guidance August 2, 2022)

Ultimately, officials hope that DARWIN EU will assist the Committee for Orphan Medicinal Products (COMP) with applications for orphan designation and support other committees with drug use studies and post-marketing studies examining safety and efficacy. long-term effectiveness of orphan drugs.

The authors acknowledge that it is often difficult to characterize the natural history of rare diseases due to small patient populations, geographically dispersed populations, and the complexity of the diseases themselves. However, they argue that the growing number of patient registries capturing real-world data (RWD) may facilitate product development for rare diseases.

Officials recognize that there are multiple challenges in collecting and analyzing data from patient registries that need to be considered.

“For example, in order to increase patient populations and the statistical power of clinical studies on these drugs, the pooling of data from different registries and/or the interoperability between these data sources is essential”, specify the authors. . “This requires that various registries collect data on a particular disease of interest to capture the same information according to adopted standard coding terminologies and list of common data elements, during the development of an orphan medical product as well as after commercialization.”

They note that to address these challenges, additional steps may be needed to improve the completeness of registry data and its accuracy to ensure that data quality is sufficient to answer specific research questions. They also said it was essential that issues such as data ownership, how to facilitate data collection, data access, data sharing and data linkage be addressed.

“All of these aspects can be difficult to implement due to the limited funding and resources available to registries, but also due to restrictions related to national data protection requirements,” the authors said. “A clear sustainability plan setting out short and long-term strategies on the development and maintenance of registries is essential to ensure their continued viability, adaptability and adequacy to support regulators’ decision-making.”

Officials said there are opportunities to address these challenges, particularly if drug sponsors and regulators engage throughout the product development lifecycle, such as deal pipeline meetings, information meetings of the working group on innovation, kick-off meetings for priority medicines (PRIME), dialogues during an orphan designation procedure, scientific advice procedures and pre-submission meetings. The article includes a graphic showing how such interactions can take place, which can help sponsors visualize when in the regulatory timeline the different meetings might take place.

“Early engagement with registry holders is an essential prerequisite for understanding the opportunities offered by registry data, but also its limitations when used to support the demonstration of significant benefits of orphan drugs and their long-term follow-up. term after clearance,” the authors said.

With these challenges in mind, officials remain optimistic that registries can successfully meet the regulatory needs of orphan drugs. They argue that registries can fill knowledge gaps by providing natural history data, standard of care information, creating historical comparison cohorts/external control arms in clinical trials and by providing long-term safety and efficacy data.

The authors caution that the suitability of a registry for regulatory purposes must be assessed on a case-by-case basis and by carefully balancing its opportunities against its limitations. Researchers will also need to consider factors such as the data elements captured, the quality of that data, and data governance. With this in mind, the authors note that researchers should read the EMA guidelines on registry-based studies which recommend performing a feasibility and quality management analysis.

“At an early stage, collaboration between pharmaceutical companies and registry holders will help understand the suitability of the registry to answer a specific research question,” the officials said. “The multiple initiatives launched at European and international levels will provide frameworks to promote the values ​​of registries from the perspective of all stakeholders.

“Early and ongoing dialogue facilitates the sharing of experiences and best practices to help further improve the quality of registries and enable their full exploitation in drug research, development and monitoring for faster patient access to innovative treatments,” they added.

Frontiers in pharmacology

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