Study: FDA approves more orphan drugs with specific cancer, pediatric indications over EMA
The US Food and Drug Administration (FDA) is more likely to approve drugs with an orphan designation that were indicated for subgroups of cancer or pediatric indications than the European Medicines Agency (EMA), the results of a recent cross-sectional study suggest.
Enrico Costa, of the Italian Medicines Agency (AIFA) and the Program On Regulation, Therapeutics, And Law (PORTAL) at Brigham and Women’s Hospital and Harvard Medical School, and colleagues said FDA licensed nearly all approved products with an orphan drug designation between 2011 and 2020. FDA and EMA both approved more than one-third of the total orphan drugs in both regions, about one-third of orphan drugs were approved by FDA only, and less than one-third of FDA-approved drugs with an orphan drug designation were approved in the European Union (EU) without that designation, they noted.
“These findings reflect the differing regulatory frameworks and practices between the United States and the EU, and highlight how the US system’s indication-based structure guides Orphan Drug designations toward a broader range of conditions and specific disease subsets, including covering cases in which therapeutic uses of already marketed products from common diseases were applied to rare diseases,” Costa and colleagues said.
Costa and colleagues conducted a cross-sectional study of 344 rare disease drug approvals by both FDA and EMA between 2011 and 2020, comparing the differences in whether and how drugs were approved by each regulator. They noted when a regulator approved a product using the orphan drug designation, if it was approved without that designation, and when one regulator approved a drug that was not approved by the other.
The authors found 336 rare disease approvals (97.7%) received an orphan drug designation from FDA, 139 approvals (40.4%) received an orphan drug designation from the EMA, and 131 approvals (38.1%) received the designation from both regulators. The most common therapeutic areas for approval across both FDA and EMA were for advanced therapies (75.0%) and genetic diseases (55.4%) followed by endocrine and metabolic diseases (69.7%), respiratory diseases (63.6%), and hematologic malignancies (56.7%), the researchers said.
In addition, the EU had 103 drug approvals (29.9%) from this list that did not have an orphan drug designation. More than one-third (36.9%) of these drug approvals did not quality for an orphan drug designation in the EU because they were “not considered distinct medical entities,” the authors said, and included cancer subgroups such as EGFR- or ALK-positive non-small cell lung cancer, specific cancer disease stages, as well as pediatric indications for more common conditions such as hepatitis C virus and HIV. EMA also determined that more than one-third of products (34.9%) did not meet the orphan drug designation threshold for significant benefit over existing treatments for hematological malignancies and non-oncological hematological diseases.
Of 110 products (32.0%) where only one agency issued the approval, 102 products (29.7%) were approved by FDA, and 8 products (2.3%) were approved by EMA. The reasons for products not being approved by EMA included not submitting a marketing application (86.3%) and an issue related to benefit and risk (13.7%).
For products without submitted marketing applications, 40.9% were new active substances, and the rest were products already approved in the EU but would have been new indications, combinations, or dosage forms. The authors noted that it is not clear why EMA approval was not sought for products without submitted marketing applications.
The differences come down to the incentives outlined in each region’s respective orphan drug legislation, the authors said. While both the US and Europe offer 10 years of market exclusivity for orphan drug products, the European legislation does not offer tax credits for clinical trials, contains a different disease prevalence threshold, is meant for life-threatening or chronically debilitating rare conditions, and requires the drug to have a significant benefit over existing treatments.
The result is that the US orphan drug legislation may not have led to much additional incentive on its own, but instead has created a framework that “allowed a broader range of conditions to qualify for the designation, notably including cancer,” Costa and colleagues said.
The authors also noted that fewer orphan drug designations in the region have not necessarily meant that patients with rare diseases in Europe receive worse care or limited access to effective drugs.
Costa and colleagues said their analysis “may help regulators and policymakers implement necessary legislative and procedural changes to prioritize rare diseases within orphan incentives, while creating specific pathways to address the challenges posed by scientific advancements and other societal needs.”
