TY - JOUR
T1 - Challenges and opportunities in NASH drug development
AU - Harrison, Stephen A.
AU - Allen, Alina M.
AU - Dubourg, Julie
AU - Noureddin, Mazen
AU - Alkhouri, Naim
N1 - Publisher Copyright:
© 2023, Springer Nature America, Inc.
PY - 2023/3
Y1 - 2023/3
N2 - Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), represent a growing worldwide epidemic and a high unmet medical need, as no licensed drugs have been approved thus far. Currently, histopathological assessment of liver biopsies is mandatory as a primary endpoint for conditional drug approval. This requirement represents one of the main challenges in the field, as there is substantial variability in this invasive histopathological assessment, which leads to dramatically high screen-failure rates in clinical trials. Over the past decades, several non-invasive tests have been developed to correlate with liver histology and, eventually, outcomes to assess disease severity and longitudinal changes non-invasively. However, further data are needed to ensure their endorsement by regulatory authorities as alternatives to histological endpoints in phase 3 trials. This Review describes the challenges of drug development in NAFLD–NASH trials and potential mitigating strategies to move the field forward.
AB - Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), represent a growing worldwide epidemic and a high unmet medical need, as no licensed drugs have been approved thus far. Currently, histopathological assessment of liver biopsies is mandatory as a primary endpoint for conditional drug approval. This requirement represents one of the main challenges in the field, as there is substantial variability in this invasive histopathological assessment, which leads to dramatically high screen-failure rates in clinical trials. Over the past decades, several non-invasive tests have been developed to correlate with liver histology and, eventually, outcomes to assess disease severity and longitudinal changes non-invasively. However, further data are needed to ensure their endorsement by regulatory authorities as alternatives to histological endpoints in phase 3 trials. This Review describes the challenges of drug development in NAFLD–NASH trials and potential mitigating strategies to move the field forward.
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U2 - 10.1038/s41591-023-02242-6
DO - 10.1038/s41591-023-02242-6
M3 - Review article
C2 - 36894650
AN - SCOPUS:85149448890
SN - 1078-8956
VL - 29
SP - 562
EP - 573
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -