Changes in revenues associated with antimicrobial reimbursement reforms in Germany

The study investigates whether recent German reimbursement reforms for novel antimicrobials operate as an effective pull incentive relative to delinked models. In particular, it asks if Germany’s exemption of designated "reserve" antibiotics from certain benefit assessments and reference pricing has increased revenues sufficiently to meet Germany’s GDP-based "fair share" of a delinked pull incentive. The context is the global antimicrobial resistance (AMR) crisis, stagnating antibiotic R&D, and G7/EU discussions on push/pull incentives. The purpose is to assess the reforms’ impact on national-level revenues for priority antibiotics and compare them to revenue targets implied by a delinked model, focusing on two reserve antibiotics also included in the UK subscription program. The importance lies in informing policy design for sustainable antibiotic innovation and access while preserving stewardship.

The paper situates the analysis within extensive literature documenting the escalating AMR burden, declining antibiotic pipelines, and the inadequacy of traditional, volume-based market incentives. It reviews push mechanisms (e.g., CARB-X, GARDP, BARDA, AMR Action Fund) and policy proposals for pull incentives that delink revenue from sales volume. It surveys international policy experimentation: the UK’s subscription model, Sweden’s access-oriented revenue guarantees, and nascent efforts in Japan, Canada, the US (PASTEUR Act), and the EU (including debates over transferable exclusivity vouchers versus revenue guarantees). The authors introduce a "fair share" framework that apportions global pull-incentive funding targets ($220–$480M annually per priority antibiotic; best estimate $310M) across high-income countries by GDP share, implying an annual German contribution of approximately $27M (about €25M). Prior work suggested German reimbursement may underpay novel antibiotics in hospital settings; this study extends the literature by testing whether post-reform Germany functions as a national-level R&D incentive.

Data were drawn from the IQVIA MIDAS database for Germany, covering Q4 2016–Q4 2022, including monthly sales volume (units, defined as standard packages), revenue (euros), and price (euro per day of treatment) for antimicrobials introduced in Europe since 2010. The analysis focuses on two antibiotics granted German "reserve" status and selected by the UK subscription: ceftazidime/avibactam and cefiderocol. An interrupted time series (ITS) analysis with seasonal autocorrelation was conducted in SAS (v9.4) using a Caswell macro to assess whether the granting of reserve status was associated with changes in levels or trends of revenue, sales volume, and price. The authors computed Germany’s annual "fair share" target from prior GDP-share estimates for G7+EU27 and compared observed revenues to the target. To estimate the price required to achieve "fair share" without changing volumes, they divided the annual "fair share" amount by current average annual sales volume to derive target unit prices and corresponding price multipliers. They also projected whether each drug could meet 10-year cumulative "fair share" revenues during market exclusivity by extrapolating average monthly revenues (accounting for observed seasonality) linearly to patent end (assumed 10 years post-EMA approval).

• Germany’s GDP-based best-estimate "fair share" target is about $27M (~€25M) per priority antibiotic annually over 10 years. • ITS analysis found that granting reserve status did not produce a discernible impact on price, revenue, or sales volume; no consistent significant level or trend changes attributable to reserve designation were observed across the two drugs. • Current average annual revenues are low relative to targets: ceftazidime/avibactam €5,825,035; cefiderocol €5,820,612. • To meet Germany’s annual "fair share" via price alone (holding volumes constant), required median price per unit increases are large: ceftazidime/avibactam from €130.72 to €429.17 (≈3.3×); cefiderocol from €169.97 to €541.68 (≈3.2×). Median price per day of treatment in 2022 was €392.16 (ceftazidime/avibactam) and €1,019.82 (cefiderocol), with median prices declining over time in nominal terms. • Projected cumulative revenues to patent end fall far short of a 10-year "fair share" total of €250M: ceftazidime/avibactam €64,552,418 (gap €185,447,582) by 2027; cefiderocol €64,026,732 (gap €185,973,268) by 2031. • Absent substantial price increases (≈3.2–3.3×), large volume growth, or a delinked top-up, German reforms do not deliver revenues comparable to a delinked pull incentive.

The findings indicate that Germany’s reimbursement reforms, including reserve status with exemptions from certain benefit assessments and reference pricing, have not meaningfully increased sales volumes or revenues for the examined reserve antibiotics, and thus do not meet Germany’s "fair share" contribution toward a delinked pull incentive. Price-only strategies sufficient to close the gap would require 3.2–3.3× increases, which could conflict with stewardship objectives and may be politically or administratively challenging without further reforms. Substantial volume increases would similarly raise stewardship concerns by potentially accelerating resistance. Consequently, to align with international consensus on supporting antibiotic innovation, Germany could: (1) implement a delinked revenue guarantee domestically to top up observed sales-based revenues; or (2) maintain current reimbursement policies while contributing to an EU-level delinked pull mechanism based on revenue guarantees rather than transferable exclusivity vouchers. These options would better support innovation while preserving stewardship by decoupling revenues from use.

German reimbursement reforms to date have not generated revenues for reserve antibiotics sufficient to meet Germany’s GDP-based "fair share" targets for delinked pull incentives. Achieving comparable impact through pricing alone would require increases of roughly 3.2–3.3× at current volumes, or alternatively substantial growth in utilization, both of which raise feasibility and stewardship concerns. Policy paths forward include adopting a delinked revenue guarantee at the national level to top up sales revenues or supporting an EU-operated delinked incentive. Future work should assess impacts once price negotiations conclude for reserve drugs, expand analyses to additional antibiotics and settings, incorporate inflation and evolving push-funding levels into fair-share calibration, and evaluate the effects of prospective EU-level pull mechanisms on German access and innovation incentives.

• Data limitations: IQVIA MIDAS provides commercial sales estimates (sampled and projected), with Germany-specific coverage from Q4 2016–Q4 2022 only. • Scope: Analysis centers on two reserve antibiotics (ceftazidime/avibactam, cefiderocol) though five have reserve status; results may not generalize to all reserve antibiotics. • Timing: The full impact of reforms may not yet be observable; price negotiations for the study drugs were incomplete during the observation window. • Methodological assumptions: ITS cannot definitively establish causality; projections assume linear trends and constant seasonality; prices were not adjusted for inflation, potentially understating real price declines. • Fair-share calibration: GDP shares and target ranges were based on 2019 data and do not incorporate inflation adjustments, variations in push funding, or national revenue outside formal pull programs.