Stephen A.Harrison1 2, Mustafa R.Bashir3, Kyoung-JinLee4, JenniferShim-Lopez4, JonathanLee4, BrandeeWagner4, Nicholas D.Smith4, Hubert C.Chen4, Eric J.Lawitz56
1. Summit Clinical Research, San Antonio, TX, USA
2. Pinnacle Clinical Research, San Antonio, TX, USA
3. Duke University Medical Center, Durham, NC, USA
4. Metacrine, Inc., San Diego, CA, USA
5. Texas Liver Institute, San Antonio, TX, USA
6. University of Texas Health San Antonio, San Antonio, TX, USA
Received 19 October 2020, Revised 28 January 2021, Accepted 29 January 2021, Available online 11 February 2021.
- The benefit of FXR agonism in patients with NASH has been clinically validated.
- However, improvements in efficacy/tolerability for the therapeutic class have been elusive.
- MET409, a novel non-bile acid agonist, resulted in a class-leading 12-week relative liver fat reduction of 38–55%.
- MET409 resulted in differentiated pruritus and LDL-cholesterol profiles – issues that have hampered FXR development.
- Data provide first evidence that the risk-benefit profile of FXR agonists can be enhanced through structural optimization.