316 Paradigm Shifting Beneficial Effects of TLANDO (Oral Testosterone) on Liver

Abstract

Oral Testosterone, methyltestosterone (e.g., Testred), was approved in 1941 and indicated as a testosterone replacement therapy (TRT) in males with a deficiency or absence of endogenous testosterone. Its prolonged use has been severely limited because of the development of liver disease, such as peliosis hepatis, hepatic neoplasms, hepatocellular carcinoma cholestatic hepatitis, and jaundice.There are significant overlapped co-morbidities between male hypogonadism and non-alcoholic fatty liver disease (NAFLD): obesity, hypertension, type 2 diabetes, and metabolic syndrome. TLANDO, a novel oral TRT containing Testosterone Undecanoate (TU) lymphatically delivered, is currently under regulatory review for marketing approval. To evaluate the effect of TLANDO on liver safety in prolonged use and to assess beneficial effects of TLANDO in hypogonadal patients with fatty liver disease. To evaluate liver safety of TLANDO (oral TRT) in chronic use, a 52-week, multi-center, open-labelled, active controlled (topical T) study was performed in hypogonadal men (N=315) in the SOAR trial (NCT02081300). Serum liver enzymes were measured at each visit (7 visits through 52 weeks) and analyzed. To assess liver beneficial effects of TLANDO, a 16-week open-label, multi-center, single arm study was performed in the Liver Fat Study (LFS: NCT03868059) with TLANDO (225mg BID fixed dose) in hypogonadal subjects (N=36). Liver fat % was measured by the Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) technique.