No Liver Toxicity Seen in TRT Study Data Presented at ENDO 2021

The testosterone replacement therapy (TRT) testosterone undecanoate oral capsules shows no evidence of liver toxicity, according to data from a two-year, multi-center study presented at ENDO 2021.

Marketed under the brand name JATENZO® by Clarus Therapeutics, Inc., this oral softgel has been commercially available since February 2020 after a March 2019 approval by the U.S. Food and Drug Administration. It remains the only FDA-approved oral softgel for TRT in adult hypogonadal males who have low or no testosterone due to certain medical conditions.

“Prior to the launch of JATENZO, the only approved oral TRT formulation in the U.S. — methyl-testosterone (alkylated androgen) — was associated with significant liver toxicity,” says Endocrine Society member Ronald S. Swerdloff, MD, MACP, lead study author and senior investigator at the Lundquist Institute at Harbor-UCLA. “These results are significant because they provide adult men with hypogonadism an oral option that is not only effective in maintaining normal testosterone levels, but also has no evidence of damage to the liver.”

The two-part study evaluated two years of twice-daily JATENZO use in hypogonadal men (two serum T ≤ 300 ng/dL) aged 18-75 years. The first study followed patients for 12 months; 86 men from the first study then enrolled in the second study, which lasted another year. The analysis found that JATENZO use:

• Kept total testosterone levels in the normal range with a safety profile that is relatively consistent with other forms of TRT.
• Demonstrated no clinically significant change in liver function tests – no clinically significant changes in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminases (ALT), and bilirubin levels.
• Showed small, yet statistically significant, increases in prostate-specific antigen (PSA), a protein produced by the prostate, and hematocrit (HCT), which measures red blood cell levels. These increases are observed with other TRTs, regardless of mode of administration.
• Had minimal effects on LDL (“bad”) cholesterol and lowered HDL (“good”) cholesterol, which is common among other TRTs.

“We launched JATENZO to provide men with low testosterone an effective oral option that avoids some of the drawbacks of other routes of administration, such as injection-site pain or testosterone transference to partners and children, without harmful effects on the liver,” says Endocrine Society member Bob Dudley, PhD, chairman, CEO and president of Clarus Therapeutics. “We’re thrilled with these long- term results that continue to show we achieved that goal, and that JATENZO can offer a long-term therapeutic benefit for many patients.”

The primary efficacy variable in the analysis was the change from baseline of total testosterone (T). The key safety variables included change in blood pressure (BP), including both systolic and diastolic BP; HCT, prostate variables, such as PSA and prostate function, via The American Urological Association International Prostate Symptom Score (AUA-IPSS); and liver function tests, including ALP, AST, ALT, and bilirubin.