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LPCN 1144 Resolves Non-Alcoholic Fatty
Somaya Albhaisi1, Kilyoung kim3,
Jonathan Baker3, Nachiappan Chidambaram3, Mahesh V. Patel3, Michael Charlton4, Arun
1. Dept of Internal Medicine, VCU, Richmond,
2. Div. of Gastroenterology, Hepatology
and Nutrition, Dept. of Internal Medicine, VCU, Richmond, VA, USA
3. Lipocine Inc., Salt Lake City, UT, USA.
4. University of Chicago Medicine, Chicago,
Hypogonadism, defined by low circulating testosterone (T) levels, is increasingly being recognized in those with metabolic
syndrome, the principal risk factor for nonalcoholic fatty liver disease (NAFLD). Low T states are also seen in males with NAFLD.
However, it was not known if T replacement corrects NAFLD in these individuals.
To determine (1) the prevalence of NAFLD in hypogonadal males, and (2) the effect of T-replacement on underlying NAFLD in hypogonadal
A multicenter open label single-arm 16-week study of LPCN 1144, a testosterone prodrug, in hypogonadal males (n=138) was performed
with a subset (n=36) participating in liver fat assessment (NCT 03868059). Liver fat was assessed by MRI-PDFF and liver injury
from AST, ALT and GGT. NAFLD resolution was defined by MRI-PDFF > 5% from baseline to end of study < 5%. The effects of LPCN
1144 on liver enzymes were observed in the study of androgen replacement (SOAR) (NCT 02081300).
Results: (1) Prevalence in hypogonadal males: NAFLD prevalence, defined by MRI-PDFF
> 5% was 62%, which is higher than that reported in the general population (Browning et al, Hepatology 2004). (2) Effect
of LPCN 1144 on NAFLD: NAFLD resolved in 33% of subjects at 8 weeks (mean relative reduction (RR): 45%) and 48% (mean RR: 55%)
by 16 weeks after starting LPCN 1144. The reduction in liver fat was greatest in those with highest baseline liver fat (BL
5%: 71%, BL 8%: 80%, BL 10%: 75%). Normalization rate of ALT and GGT were 100% and 50% of LPCN-1144 treated
patients respectively. Those with potential NASH (BL 8%, n=10) had greater reduction in AST (mean change: -2.5
U/L vs +0.3 U/L), ALT (-2.0 U/L vs -0.5 U/L) and GGT (-15.4 U/L vs -7.1 U/L) compared to the population as a whole. Similar findings
were observed with the SOAR trial with normalization of liver enzymes in subjects with elevated
liver markers (ALT 52%, AST 50%, GGT 31%) but interestingly more significant for ALP (67%). No major adverse events occurred with
the use of the study drug.
Male hypogonadism is associated with NAFLD. Administration of the T-prodrug LPCN 1144 resolved NAFLD in half the affected patients
and normalized liver injury markers in those with elevated levels without any safety signals. These results warrant further assessment
of LPCN 1144 for the treatment of NASH in males with low T levels.