(313) To be an Orphan Disease or Not to Be: An Evaluation of Prevalence Estimates for Cancers Near the Orphan Status Threshold and Implications for Orphan Drug Planning

Background: Orphan Drug Programs are designed to incentivize research and therapeutic development for orphan diseases, which are defined as a disease with prevalence less than 5 per 10,000 (European Union [EU]) or a prevalence less than 200,000 people (United States [US]). The number of orphan diseases ranges from 7,000 to 10,000 affecting up to 60 million patients in the EU and US, and potentially 400 million patients worldwide. Oncology outcomes have received the most orphan disease designations and orphan drug approvals. Changes in prevalence of specific cancers over time may affect orphan designation.

Objectives: To identify examples of selected cancers that have a prevalence near the threshold of orphan disease designation in the EU and US, to describe trends in these cancers, and to discuss implications for orphan designation and drug policies.

Methods: Complete prevalence data for available cancer types were estimated using publicly available sources. For the EU-27, complete prevalence of cancers in 2020 was extracted from the European Cancer Information System. For the US, complete prevalence of cancers was estimated using the US National Cancer Institute’s SEER program with ICD-O-3/WHO 2008 site recodes; age- and gender-specific limited-duration prevalence for 2000, 2010, and 2020 was calculated using the SEER*STAT software and converted to complete prevalence with SEER’s ProjPrev and ComPrev softwares.

Results: In the EU-27, cancers that would have met the orphan disease threshold in 2010 but not 2020 included: brain and neuroepithelial (2010: 3.94; 2020: 5.08 per 10,000) and small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) (2010: 4.59; 2020: 6.04 per 10,000). Cancers close to the threshold in 2020 included plasma cell/multiple myeloma (4.32 per 10,000) and soft tissue (3.96 per 10,000). In the US, cancers that previously would have been considered orphan diseases that are now above US threshold include CLL (2000: 88,678; 2020: 208,934), ovarian (2000: 183,068; 2020: 226,306), and Hodgkin lymphoma (2000: 128,994; 2020: 206,977).

Conclusions: Understanding cancer prevalence trends may help elucidate the impact of prevalence increases on future orphan drug designation and therapeutic development. Current orphan designation definitions do not account for population increases (US only), age distribution changes, or extended duration of disease; these definitions may inadvertently reduce new therapeutic development for rare disease patient populations with prevalence near the threshold.