Which drugs will Medicare negotiate next? Predicting selected drugs for Initial Price Applicability Year 2029.

BACKGROUND: The fourth cycle of the Medicare Drug Price Negotiation Program (MDPNP) for Initial Price Applicability Year (IPAY) 2029 will continue to include both Medicare Part B and Part D drugs while incorporating several important policy changes that affect eligibility and selection. These changes, including clarification of drug eligibility criteria, expiration of the temporary small biotech exception, and implementation of the biosimilar delay provision, may substantially influence which drugs are selected for negotiation. OBJECTIVE: To predict the Medicare Part B and Part D 20 drugs most likely to be selected for IPAY 2029. METHODS: Using the Centers for Medicare & Medicaid (CMS) Medicare Part B and Part D drug-spending data from 2020 through 2024 and Average Sales Price 2025 pricing files, we projected 2025 gross Medicare expenditures (GMEs) using regression models incorporating historical use and pricing trends. Statutory exclusion criteria were applied consistent with the Inflation Reduction Act, the One Big Beautiful Bill Act, and the June 2026 CMS proposed rules to identify negotiation-eligible drugs and rank drugs by projected GME. A secondary forecasting approach incorporating unadjudicated quarterly Medicare Part B and Part D spending data through quarter 3 of 2025 was conducted to approximate the statutory CMS expenditure assessment period (November 1, 2025-October 31, 2026). RESULTS: Fifty qualifying single-source drugs were identified. Twenty drugs, each with projected 2025 GMEs exceeding $500 million, were predicted to be selected for IPAY 2029. The primary and secondary forecasting approaches identified similar results, with 17 of the top 20 drugs appearing in both. Three drugs became newly eligible following expiration of the temporary small biotech exception. We also identified 27 drugs with projected 2025 GMEs exceeding $1 billion that remained ineligible because of statutory time on market or orphan drug exclusions as well as additional drugs potentially affected by the biosimilar delay provision. CONCLUSIONS: Recent legislative and regulatory changes continue to reshape eligibility for the MDPNP. These findings provide an updated framework for anticipating future negotiation cycles and demonstrate how evolving CMS policy may influence drug selection and the future implementation of the MDPNP.