Partial Orphan Cancer Drugs: US Food and Drug Administration Approval, Clinical Benefit, Trials, Epidemiology, Price, Beneficiaries, and Spending.

OBJECTIVES: The Orphan Drug Act (ODA) incentivizes drug development for rare diseases with limited sales potential. Partial orphans-drugs used to treat rare and common diseases-frequently turn into multi-billion dollar blockbusters. This study analyzes partial orphan cancer drugs' development, approval, and economics.

METHODS: 170 drugs with US Food and Drug Administration approval for 455 cancer indications were identified (2000-2021). 110 full, 22 partial, and 38 non-orphan drugs were compared regarding their approval, benefits, trials, epidemiology, price, beneficiaries, and spending with data from regulatory documents, Global Burden of Disease study, and Medicare and Medicaid.

RESULTS: Full orphans, relative to partial and non-orphans, were more frequently monotherapies for hematologic cancers supported by smaller single-arm trials treating diseases with a lower incidence and higher severity. The time from first to second indication approval was 1 year shorter for partial than full orphans. Full orphans offered a greater overall survival (median: 4.0 vs 2.8 vs 2.8 months, P < .001) and progression-free survival benefit (median: 5.1 vs 2.5 vs 3.6 months, P < .001). Monthly prices were higher for full and partial than non-orphan drugs (median: $17 177 vs $13 284 vs $12 457, P < .001). Beneficiaries (8790 vs 4390 vs 1730) and spending ($570 vs $305 vs $156 million) per drug were greater for partial than non-and full orphans.

CONCLUSIONS: Although partial orphans' benefits, trials, and economics are more similar to non-than full orphans, they receive all of the ODA's benefits and are swiftly extended to new indications; resulting in greater spending. A maximum ODA revenue/patient threshold could limit expenditure on partial orphans.