Payer and Manufacturer Agreements for High-Cost Therapy: A Narrative Review

Abstract

Between 2022 and 2025, several ultra–high-cost, one-time therapies were approved in the United States, offering potentially curative options for conditions such as spinal muscular atrophy, hemophilia, and sickle cell disease. Despite their clinical value, upfront costs often exceeding $2-4 million create major challenges for payers, especially Medicaid programs with fixed budgets. Traditional reimbursement models, designed for chronic therapies, may not align with the long-term benefits and financial risks of these treatments. This has led to growing interest in alternative payment models, including outcomes-based agreements, installment payments, and risk-sharing contracts. However, adoption remains inconsistent due to regulatory barriers, administrative complexity, and limited long-term data. A narrative literature review was conducted to evaluate U.S. pricing strategies and manufacturer–payer payment models for ultra–high-cost, one-time therapies. Peer-reviewed and grey literature were identified through searches of PubMed, Embase, and Google Scholar, along with policy and regulatory sources. Publications from 2010 to 2025 were included and synthesized to categorize payment models and identify implementation challenges. Manufacturers used diverse pricing approaches rather than a single model. Outcomes-based agreements were more common when clinical endpoints were measurable, while other therapies relied on lump-sum payments with support programs. Adoption varied based on therapy characteristics and payer preferences, with limited standardization across stakeholders. These therapies are financed through a mix of traditional and alternative models, but regulatory and operational barriers continue to limit widespread adoption.