Uptake of orphan drugs in the WHO essential medicines lists

Abstract

Objective We evaluated the uptake of medicines licensed as orphan drugs by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) into the WHO Model list of essential medicines and the WHO Model list of essential medicines for children from 1977 to 2021. Methods We collated and analysed data on drug characteristics, reasons for adding or rejecting medicines, and time between regulatory approval and inclusion in the lists. We compared trends in listing orphan drugs before and after revisions to the inclusion criteria of the essential medicines lists in 2001, as well as differences in trends for listing orphan and non-orphan drugs, respectively. Findings The proportion of orphan drugs in the essential medicines lists increased from 1.9% (4/208) in 1977 to 14.6% (70/478) in 2021. While orphan drugs for communicable diseases have remained stable over time, we observed a considerable shift towards more orphan drugs for noncommunicable diseases, particularly for cancer. The median period for inclusion in the essential medicines lists after either FDA or EMA first approval was 13.5 years (range: 1–28 years). Limited clinical evidence base and uncertainty about the magnitude of net benefit were the most frequent reasons to reject proposals to add new orphan drugs to the essential medicines lists. Conclusion Despite lack of a global definition of rare diseases, the essential medicines lists have broadened their scope to include medicines for rare conditions. However, the high costs of many listed orphan drugs pose accessibility and reimbursement challenges in resource-constrained settings.

Refocusing the World Health Organization’s Model List of Essential Medicines on the needs of low and middle income countries

“…In the wake of the development of targeted therapy and escalating prices of new medicines, an increasing number of upper middle and high income countries have adopted the essential medicines concept, usually to define reimbursement in their health insurance systems 23. As a result, WHO has received an increasing number of applications for new medicines to be added, including high priced products that require specialised delivery and medicines for rare diseases 610…”

“…The inclusion of many high priced medicines over the past decade has prompted debate about the focus and purpose of the list. Difficult questions have been raised as to whether high priced medicines, especially those that require highly specialised healthcare service delivery, should be included when most countries, especially in resource constrained settings, are not in a position to safely use such medicines and ensure sustainable financing 6. Some people have proposed that a separate list of essential medicines for rare diseases be developed 7.…”