In 2022, Medicare alone spent 42. 1 billion on prescription drugs, with antineoplastic and classical hematology drugs accounting for 44% and 8% of the total, respectively 1. While antineoplastic drugs dominate discussions of rising pharmaceutical costs in the United States (US) 2, classical hematology drugs have received comparatively little attention. In recent years, classical hematology as a field has undergone a tremendous transformation and increasing recognition 3, marked by accelerated approvals by the US Food and Drug Administration (FDA), a shift toward biologics and biosimilar medications, and the emergence of ultra-high-cost gene therapies 4. Given this inflection point in the management paradigm of classical hematology conditions, we sought to characterize the FDA approvals of classical hematology drugs over the last 30 years and specifically to examine current costs and sales in the US. We identified all classical hematology drugs approved by the FDA between January 1, 1995, and December 31, 2024. Classical hematology drugs were defined as medications prescribed by hematologist-oncologists for non-malignant indications. Drugs were categorized as novel pharmaceuticals (synthesized from chemical compounds), biologics (derived from living organisms), and biosimilars (highly similar, but not identical, to biologics previously approved) 5. Gene therapies were analyzed as a distinct subgroup. Cost estimates for 2024 were based on wholesale acquisition costs (WAC). For continuous-duration therapies, annual WACs were used, whereas for fixed-duration therapies, the WAC of a typical treatment course was calculated. This approach allowed standardized cost comparisons across drugs with varying dosing schedules, durations of therapy, and clinical indications. WACs and US total gross sales data of these drugs for 2024 were obtained from IPD Analytics (Aventura, FL) 6. Over the 30-year study period, 98 classical hematology drugs were approved by the FDA (Table S1). Approvals increased markedly over time, with 11% approved between 1995 and 2004, 29% between 2005 and 2014, and 60% between 2015 and 2024. Pharmaceuticals accounted for 32% of approvals, biologics for 58%, and biosimilars for 10%. Most of the biologic and biosimilar approvals (64%) occurred in the last decade, underscoring a progressive shift away from novel pharmaceuticals toward complex biologic therapies. Six gene therapies were approved including three for hemophilia and one each for sickle disease, beta thalassemia, and sickle cell disease/beta thalassemia (dual indication). Approved drugs spanned a broad range of indications. The most common categories were bleeding disorders (31%), anemia (30%), neutropenia (9%), and thrombocytopenia (9%). By diagnosis, hemophilia accounted for 25% of approvals, followed by chemotherapy-induced neutropenia (9%), thromboembolism (8%), paroxysmal nocturnal hemoglobinuria (PNH; 7%), anemia of chronic kidney disease (6%), iron deficiency anemia (6%), and immune thrombocytopenia (5%). Notably, several ultra-rare diseases with relatively small patient populations (prevalence of < 1 in 50 000 population), such as PNH and atypical hemolytic uremic syndrome, were associated with multiple high-cost biologics, reflecting both unmet clinical need and favorable regulatory incentives for orphan drug development 7. Costs varied widely by indication and treatment. Gene therapies had a median cost of 2. 9 million per treatment (range, 2. 2–3. 5 million). Among non-gene therapies, the most expensive drugs are shown in the Table 1. Fixed duration therapies had a median cost of 3000 per course (range, 64–378 000), whereas continuous-duration therapies had a median annual cost of 467 000 (range, 2400–1. 8 million). The most expensive fixed-duration treatment was emapalumab for hemophagocytic lymphohistiocytosis, with a cost of 378 000 for an 8-week course, while the most expensive continuous-duration treatment was pozelimab for CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE syndrome), with an annual cost of 1 800 000. Diseases with the most expensive drugs, compared to gene therapy, are shown in Figure 1. Continuous-duration treatments for hemophilia were particularly costly, with a median annual cost of 630 000 (range, 270 000–853 000). Such therapies are often initiated early in life, amplifying lifetime costs. Despite their high per-patient costs, gene therapies accounted for only a small fraction of overall classical hematology drug sales, reflecting a relatively slower uptake. The estimated 2024 US gross sales across all classical hematology drugs exceeded 70 billion, whereas the combined sales of all gene therapies totaled only 143 million (Figure 2). Thromboembolism treatments, including prophylactic indications, dominated total sales at 43. 5 billion, representing more than half of all expenditures. This disproportionate contribution reflects the high prevalence of thromboembolic diseases, long treatment durations, and expanding indications for anticoagulant use across medical specialties. Other high-revenue indications included hemophilia (6. 9 billion), immune thrombocytopenia (4. 9 billion), PNH (4. 7 billion), chemotherapy-induced neutropenia (2. 8 billion), anemia of chronic kidney disease (2. 0 billion), and iron deficiency anemia (1. 8 billion). Six drugs (indication, year approved, year discontinued) were discontinued during the study period, most commonly for financial reasons (betrixaban: thromboembolism, 2017, 2020; daprodustat: anemia of chronic kidney disease, 2023, 2024; fidanacogene elaparvovec: hemophilia B, 2024, 2025; oprelvekin: immune thrombocytopenia, 1997, 2011), and two were withdrawn for safety concerns (peginesatide: anemia of chronic kidney disease, 2012, 2013; voxelotor: sickle cell disease, 2019, 2024). These findings highlight several important trends in classical hematology. First, FDA approvals have accelerated dramatically over the past three decades, with nearly two-thirds occurring in the most recent decade. Second, biologics and biosimilars now comprise most approved agents, reflecting both scientific advancements and evolving regulatory pathways. Third, although gene therapies represent a major therapeutic innovation, their current uptake and financial footprint remain modest compared with chronic therapies for common conditions such as thromboembolism. In contrast, continuous-duration treatments for rare hereditary disorders such as hemophilia impart a substantial and sustained financial burden, with annual per-patient costs often exceeding 500 000. If gene therapies demonstrate durable efficacy and long-term safety, they may ultimately offer a cost-effective alternative to lifelong treatment, despite their high upfront prices. Our study has limitations. Some drugs included in the analyses have non-classical hematology indications, such as direct oral anticoagulants used for atrial fibrillation or luspatercept for myelodysplastic neoplasms. In addition, certain agents are frequently prescribed by non-classical hematologists, including erythropoiesis-stimulating agents by nephrologists and granulocyte colony-stimulating factors by medical oncologists. We were unable to disaggregate sales by treatment indication or prescriber subspecialty, which may have led to overestimation of sales attributed to classical hematology. Finally, WAC-based cost estimates do not reflect negotiated discounts or rebates, although they provide a consistent benchmark for cross-drug comparisons. In conclusion, classical hematology drugs contribute substantially to US prescription drug spending, with over 70 billion in annual sales and costs concentrated in therapies for thromboembolism and rare hereditary disorders. As innovation continues to accelerate, balancing therapeutic advances with affordability and equitable access will be a central challenge for clinicians, policymakers, and healthcare systems in classical hematology. Jithma P. Abeykoon, Lewis T. Go, Lucas T. Go, and Ronald S. Go designed the research, analyzed the data, and wrote the manuscript. Alexandra P. Wolanskyj-Spinner, Michelle A. Elliott, Rachelle L. Rouse, Chelsee J. Jensen, Leslie J. Padrnos, Rajiv K. Pruthi, Candido E. Rivera, Surbhi Shah, Marwan E. Shaikh, Mustaqeem A. Siddiqui, Meera Sridharan, and Ewa M. Wysokinska critically appraised the manuscript and reviewed the data; and all authors approved the manuscript. This project was supported by the generosity of the Joseph F. and Mary M. Fleischhacker Family Foundation and Dr. Kenneth G. Mann. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Table S1: FDA-approved drugs in classical hematology (1995–2024). 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Go et al. (Sat,) studied this question.