Abstract

Approvals, clinical significance, and prices of antibiotics: The evidence on value-based innovation

Rosa Rodriguez-Monguio, PhD, MS¹, Enrique Seoane, PhD ², John Powers, MD FACP FIDSA³ (1)University of California San Francisco, (2)Chapman University, (3)University of Maryland School of Medicine

APHA 2022 Annual Meeting and Expo

Background: The lack of antibiotic innovation has been credited to market failures, inadequate reimbursement, and lower revenue prospects that discourage the development of new antibiotics. We assessed long-term trends in antibiotics approvals and market discontinuations, comparative effectiveness, prices at market entry, and unit sales of systemic antibiotics approved by the US Food and Drug Administration (FDA) in 1980-2021.
Data and Methods: We collected regulatory data from the FDA website, FDA regulatory actions published in the Federal Register, and sponsor companies’ financial reports. We performed analyses pre- and post- enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA, 2012) that established the qualified infectious disease product (QIDP) designation to expedite the development of new antibiotics.
Results: In the study period, the FDA approved 77 antibiotics, of which 46 (59.7%) were marketed and 31 (40.3%) were discontinued as of December 31, 2021. Antibiotic discontinuations for financial reasons represented 80.6% of all discontinuations. The FDA approved most antibiotics for indications with multiple therapeutic alternatives already marketed in the US, including pneumonia (11 antibiotics), acute bacterial skin and skin structure infections (8), and urinary tract infection (6). All 15 QIDP antibiotics were tested using non-inferiority clinical trials. Pivotal clinical studies reviewed by the FDA did not show a statistically significant difference in clinical outcomes between QIDP and already marketed antibiotics. Prices at market entry of new antibiotics increased between 24 and 62 times in the period 1980-2021. There were 9 (52.9%) QIDP antibiotics with average annual sales below $50 million, 4 (2.35%) between $50 and $100 million, and 2 (11.7%) with average annual sales exceeding $200 million. Two companies filed for bankruptcy after marketing QIDP antibiotics.
Conclusions: More than one-third of the new antibiotics approved by the FDA in the past 40 years were discontinued from the market for financial reasons. The QIDP established by the US Congress in 2012 resulted in 14 new antibiotics without evidence of better patient outcomes compared to low-cost alternatives. The price and reimbursement of new antibiotics increased significantly during the study period. Still, lower utilization of new antibiotics may be related with evidence of added clinical benefits for patients and higher prices compared to already marketed therapeutic alternatives.