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We present a longitudinal analysis of investigational new drug applications (INDs) for new, systemic antibacterial drugs under active development between 1980 and 2019, evaluating the characteristics of these investigational drugs and the outcomes of these drug development programs. The number of INDs in active development declined by two-thirds, from 39 active INDs at its peak in 1987 to a low 13 in 2001, with decreased development of new cephalosporin, quinolone, and macrolide drugs and reduced participation from large pharmaceutical firms. Antibacterial drug development activity rebounded substantially from 2002 to 2009, primarily led by involvement of small pharmaceutical companies. As of 31 December 2019, the number of active INDs has declined to an 11-year low, and the number of antibacterial INDs initiated with the US Food and Drug Administration during 2010–2019 was lower than any of the previous 3 decades. Antibacterial drug development programs initiated in the 1980s and 1990s had high success rates, with >40% of INDs obtaining marketing approval, in a median time of about 6 years from IND receipt to approval. For drug development programs initiated between 2000 and 2009, we found that IND-to-approval rates reduced to 23%, with median development times for approved antibacterial drugs increasing to 8.2 years. The majority of INDs in development as of 31 December 2019 come from already established drug classes, most in early stages of development, and few are sponsored by large pharmaceutical companies. [ABSTRACT FROM AUTHOR]

Background As drug development has globalized, trials have increasingly enrolled participants from all parts of the world rather than just the United States and Western Europe. For antibacterial drug trials, understanding enrollment trends and regional differences is important for generalizability considerations. Methods We retrospectively analyzed 42 phase 3 trials submitted to the US Food and Drug Administration after 2001 for complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infection (ABSSSI) (n = 29 282 participants). Enrollment numbers, demographics, clinical characteristics, and microbiological data were compared to identify temporal and geographic trends. Results For cUTI, cIAI, and CABP trials, Eastern European enrollment greatly increased over the study period. For ABSSSI trials, North American enrollment increased. Demographic characteristics and regional microbiology among regions were broadly similar with several exceptions. For cIAI trials, Eastern European participants had the lowest proportion of participants with prior antibacterial drug therapy. For ABSSSI trials, North American participants more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (17.8% vs 9.0%, P  = .0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, P  = .044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, P  < .0001). Conclusions Geographic trends in recruitment for recent antibacterial clinical trials differ by indication. Regional similarities in demographic characteristics and microbiology across regions lessen concerns regarding generalizability due to shifting enrollment trends. [ABSTRACT FROM AUTHOR]

We present a longitudinal analysis of investigational new drug applications (INDs) for new, systemic antibacterial drugs under active development between 1980 and 2019, evaluating the characteristics of these investigational drugs and the outcomes of these drug development programs. The number of INDs in active development declined by two-thirds, from 39 active INDs at its peak in 1987 to a low 13 in 2001, with decreased development of new cephalosporin, quinolone, and macrolide drugs and reduced participation from large pharmaceutical firms. Antibacterial drug development activity rebounded substantially from 2002 to 2009, primarily led by involvement of small pharmaceutical companies. As of 31 December 2019, the number of active INDs has declined to an 11-year low, and the number of antibacterial INDs initiated with the US Food and Drug Administration during 2010-2019 was lower than any of the previous 3 decades. Antibacterial drug development programs initiated in the 1980s and 1990s had high success rates, with >40% of INDs obtaining marketing approval, in a median time of about 6 years from IND receipt to approval. For drug development programs initiated between 2000 and 2009, we found that IND-to-approval rates reduced to 23%, with median development times for approved antibacterial drugs increasing to 8.2 years. The majority of INDs in development as of 31 December 2019 come from already established drug classes, most in early stages of development, and few are sponsored by large pharmaceutical companies., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)