Novel oral testosterone therapy shows liver health benefits

A novel lymphatically delivered oral testosterone undecanoate (Tlando) is a fixed-dose, well-tolerated, and effective treatment for hypogonadism with liver health benefits that clearly differentiate it from the potentially hepatotoxic oral methyltestosterone, reported Irwin Goldstein, MD, at the American Urological Association 2020 Virtual Experience.

“This innovative product has exciting, paradigm-shifting potential for treating men with low testosterone,” said Goldstein, director of Sexual Medicine at Alvarado Hospital in San Diego, California, and clinical professor of surgery at the University of California San Diego.

“It offers the opportunity to provide safe, effective, and well-tolerated testosterone replacement through the oral route that is the generally preferred method for medication administration. In addition, available data indicate that it not only avoids the adverse hepatic effects that have historically limited use of oral testosterone, but it improves markers of nonalcoholic fatty liver disease [NAFLD] that is a serious and prevalent condition. Low testosterone (ie, hypogonadism) is common in males with NAFLD.”

Methyltestosterone is prone to cause liver toxicity with oral ingestion because it is directly transported to the liver through the portal vein, Goldstein said. In contrast, the lymphatically delivered oral testosterone undecanoate is a nonmethylated prodrug of endogenous testosterone, found in Tlando, that avoids first-pass metabolism in the liver and enters the systemic circulation via the lymphatics.

The safety and efficacy of Tlando for treating men with low testosterone was investigated in the 1-year SOAR trial that included 210 men who received the investigational product and a control group of 105 patients treated with topical testosterone gel.

Results from SOAR showed that the oral testosterone undecanoate was associated with a significantly greater increase in free testosterone levels compared with the topical product, and it improved key mental and sexual domains, reported Goldstein, who was an investigator in SOAR and an earlier dosing study.

Safety data in the study included measurement of liver enzymes and showed that reductions were consistently achieved in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and ɣ-glutamyl transferase among men who had elevated levels of those markers of liver injury at baseline. Rates of normalization for those 4 enzymes ranged from 31% for ɣ-glutamyl transferase to 67% for alkaline phosphatase.

40% reduction in liver fat at 4 months

Additional data on the liver effects of the novel testosterone undecanoate product were obtained in a smaller separate trial of men with hypogonadism. Using the objective Magnetic Resonance Imaging Proton Density Fat Fraction technique to measure liver fat percentage, it found that after 4 months, men with NAFLD at baseline achieved an approximately 40% reduction in liver fat. In addition, more than 75% of men who entered the study with NAFLD were considered “responders” to the oral testosterone undecanoate based on achieving a 30% or greater reduction in the percentage of liver fat.

In addition, the percentage of patients categorized as NAFLD-free rose during the study and nearly doubled by its conclusion, increasing from 34% at baseline to reach 63% at 16 weeks.

“Interestingly, the higher the baseline body mass index, the greater the reduction in liver fat achieved with Tlando treatment, and it appears that the improvement in liver fat does not appear to be explained by any decrease in body weight,” Goldstein said.

Disclosures: Lipocine Inc provided funding for the study. Goldstein is on the consultant/advisory board of Lipocine Inc, does research for AbbVie Inc and Marius Pharmaceuticals LLC, is on the Clarus Therapeutics, Inc speakers’ bureau, and receives writing support from Endo International.