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

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. 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. 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. 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. • The Orphan Drug Act (ODA) incentivizes drug development for rare diseases with limited sales potential. However, orphan drugs frequently turn into multi-billion dollar blockbusters, particularly those used to treat rare and common diseases: "partial orphans." • This is the first study to analyze the development, US Food and Drug Administration approval, epidemiology, and economics of full, partial, and non-orphan cancer drugs. • We show that the clinical benefit, trials, and epidemiology of partial orphan cancer drugs are more similar to non-orphans than full orphans. • However, partial orphans receive all of the ODA's incentives and are swiftly extended to new indications; resulting in greater prices, beneficiaries, and gross spending. • Establishing a maximum revenue threshold for the ODA's benefits alongside indication-specific pricing could reduce expenditure on partial orphan drugs. [ABSTRACT FROM AUTHOR]