A comprehensive budget impact analysis has revealed that incorporating revumenib (Revuforj; Syndax Pharmaceuticals) into health plan formularies for treating relapsed/refractory acute leukemias with KMT2A translocation would be cost-neutral over a three-year period, despite the drug's high specialty pricing. The findings challenge conventional assumptions about the economic burden of first-in-class targeted therapies for rare diseases.
Oral Administration Drives Cost Savings
The primary factor contributing to revumenib's cost neutrality is its oral formulation, which eliminates substantial administration-related expenses. "First of all, [revumenib is] a pill, so it's patient-administered. You're already not having the cost of chemotherapy administration or [intravenous] administration, which means several hours in a chair, and then the additional administration costs that that may be incurred," explained Ivo Abraham, PhD, RN, professor at the Department of Pharmacy Practice and Science, R. Ken Coit College of Pharmacy, The University of Arizona, who led the analysis.
This oral delivery mechanism removes significant expenses associated with clinic visits, infusion chair time, and direct administration costs that are substantial for traditional intravenous therapies. While patients living longer on revumenib introduces additional costs for ongoing care, these expenses are largely offset by the reduced burden of adverse events and their associated management requirements.
Challenges in Rare Disease Economic Evaluation
The analysis underscores the limitations of traditional health economic evaluation methods when applied to ultra-rare conditions. The KMT2A translocation affects only approximately 1.7 individuals per million patients, creating a minuscule patient population that strains conventional cost-effectiveness analyses.
"These are very difficult drugs to investigate," Abraham noted. "They're very expensive to make, so our old methods—old in quotes—don't help us anymore.... Most treatments that come out would not be [considered] cost-effective" based on quality-adjusted life years (QALYs).
The research team had to compare revumenib against 11 additional pharmacotherapies for relapsed/refractory acute leukemias listed in National Comprehensive Cancer Network guidelines, as no other specific treatments exist for this particular mutation. This absence of targeted comparators complicates evaluations and often requires conservative assumptions that may understate the true value proposition of novel therapies.
Budget Impact Analysis as Alternative Framework
The study demonstrates the utility of budget impact analysis as an alternative to traditional cost-effectiveness evaluations for rare disease treatments. Unlike cost-effectiveness analyses that focus on whether a drug meets conventional value thresholds, budget impact analysis examines the financial implications of introducing a new therapy onto a health plan's formulary.
"That's a key point to make, because with our health care financing, with our thinking about how to do economic evaluations, we haven't kept up with the phenomenal advances in science and clinical science, which we as a society want and value," Abraham emphasized.
This approach shifts the conversation from whether a drug is "cost-effective" by traditional metrics to how it can be made "affordable" within existing budget constraints, providing a more practical framework for payer decision-making in the era of precision medicine.
Implementation Considerations
The analysis identifies several critical factors that could influence revumenib's real-world uptake and cost-effectiveness. Building clinician confidence in the therapy emerges as paramount, since payers typically follow clinical evidence and guidance from medical professionals and key opinion leaders when making formulary decisions.
Patient adherence represents another crucial variable given revumenib's oral administration. "But the argument here is, if you treat the patient, you're going to have [good] patient quality of life—comfort—[and] no chemotherapy. There's a little bit of risk," Abraham explained. "We know that not all patients take their pills, so you have to hope that you have adherent patients, but if they are adherent, they will do well."
While good adherence leads to better patient outcomes and maintained cost-effectiveness, nonadherence could accelerate disease progression and potentially increase long-term healthcare costs, highlighting the importance of patient education and support programs in the therapy's successful implementation.
