Life Years Gained from the FDA Accelerated Approval Program in Hematology: A Portfolio Model

Background: Hematological indications form a large subgroup of therapies approved under the FDA Accelerated Approval Program (AAP), which was developed to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. The objective of this study was to estimate the population health impact of earlier access enabled by AAP in hematology indications, in terms of the number of life years gained that resulted from the therapies approved via the AAP between January 2006 and June 2021 in the United States.

Methods: A decision analytic model was developed to estimate the survival gain for each indication and to accumulate life years gained for consecutive cohorts of patients receiving hematology therapies approved through the FDA AAP between January 2006 to June 2021. The model inputs were sourced from FDA listings (Center for Drug Evaluation and Research [CDER] database for the list of AAP indications), drug labels at the time of accelerated approval (AA), FDA letters to companies, and published clinical trial data and other publications. Patient uptake of products in the AA indications was taken from the Ipsos Oncology Uptake Tool with data available until December 2022 (i.e., no patient cohorts entered the model after this date). Life year gains were estimated through June 2024 with and without the AAP, and the incremental life years gained were attributed to the program. Data on overall survival (OS) for the comparator therapy (standard of care) at the time of the AA and the relative effectiveness estimates for the new therapy were sourced from clinical trial publications. In cases of discrepancy between the AA and the regular approval (RA) trial populations, the change in indications (e.g. a line change, or narrower population) were noted, and effort was made to use efficacy data closest to that of the AA indication.

Results: In the review period (January 2006 to June 2021), 48 hematology indications were approved via the AAP. This number excludes AAs with a dose or solution change, AAs with a revised indication, and products (e.g., chimeric antigen receptor T- cell therapies) not included in the CDER database. Among the 48 indications, 24 (50%) obtained RA, 14 (29%) were withdrawn, and 10 (21%) were still ongoing as of March 2024. OS data were available for 28 indications (21 approved, 5 withdrawn, 2 ongoing), of which uptake data was available for 25. The analysis estimated that through June 2024 in the United States, 220,557 patients gained approximately a total of 144,381 life years across these 25 products due to the earlier access to therapies. The highest gains were obtained in chronic myeloid leukemia (47,653 life years, 33.0%), Hodgkin lymphoma (36,005 life years, 24.9%), and multiple myeloma (35,514 life years, 24.6%), with further gains in six other cancer types (acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma).

Conclusions: Earlier approval of drugs to treat serious conditions and fill unmet patient need is the ultimate objective of the FDA AAP. Our research shows that in hematology indications, 220,557 patients gained approximately a total of 144,381 life years across 25 products due to the earlier access to AAP therapies.

Doherty:GSK: Current equity holder in publicly-traded company; Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Benedict:Evidera: Current Employment. Martin:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Szabo:Evidera: Current Employment. Marczell:Evidera: Current Employment.