Published data show safety, efficacy of testosterone undecanoate in hypogonadism

Final data from the phase 3 MRS-TU-2019EXT trial (NCT04467697) have been published in the journal Therapeutic Advances in Urology, demonstrating the safety and efficacy of testosterone undecanoate (Kyzatrex) CIII capsules, an oral testosterone replacement therapy (TRT) for the treatment of adult men with conditions associated with a deficiency or absence of endogenous testosterone.¹

Testosterone undecanoate received FDA approval in August 2022 for the treatment of men with hypogonadism

The MRS-TU-2019EXT trial was conducted as a 6-month extension study of the phase 3 MRS-TU-2019 trial (NCT03198728), which assessed testosterone undecanoate vs a control arm in men with hypogonadism.

Overall, data from the extension study showed that 87.8% of treated patients (worse-case scenario calculations) and 96.1% of patients who completed the study achieved 24-hour eugonadal mean plasma testosterone values (222 to 800 ng/dL) at 90-day follow-up. Further, mean levels of free testosterone increased from 7.0 ng/dL to 14.1 ng/dL after 90 days of treatment.

The average serum testosterone was 452 ng/dL at 90 days, and maximum testosterone concentrations all met the FDA criteria for TRT. Eugonadal percentages were comparable for all patients regardless of age, weight, or body mass index, with diet showing no effect on percentages.

The investigators also found decreases in follicle-stimulating hormone and luteinizing hormone after 90 and 180 days of treatment, although levels did not reach 0 at either of the 2 post-baseline assessments. Additionally, the 24-hour mean change in systolic ambulatory blood pressure was 1.7 mmHg (95% CI, 0.3-3.1) after 120 days of treatment. After 190 days of treatment, systolic blood pressure (SBP) appeared stable, with a mean increase of 1.8 mmHg (95% CI, 0.3-3.2).

Regarding safety, 37.4% of patients experienced a treatment-emergent adverse events (TEAE). All TEAEs were of mild to moderate intensity, and no serious TEAEs were reported. Hypertension was the only drug-related AE observed in more than 2% of patients.

No dose increases were observed among the 36% of patients who were on existing anti-hypertensive medication at baseline. Following the start of treatment, 5 (3.2%) patients began anti-hypertensive medication, and 4 of those patients experienced a TEAE of hypertension or blood pressure increase.

By day 180, 87.1% (n = 135) of participants had completed the study. The primary reasons for study discontinuation were withdrawal (5.8%), lost to follow-up (3.9%), and other (2.6%).

"The excellent safety and efficacy data can be attributable to KYZATREX's innovative and elegant formulation,” said study author Om Dhingra in a news release on the data.² “This formulation utilizes phytosterols as a first in a pharmaceutical product to help make safe and effective oral testosterone a reality. We have expanded the traditional framework, as well, when considering effects of [sex hormone binding globulin] (SHBG) and free testosterone, which potentially mark a new era in treatment focused on usable testosterone, not just total T. We look forward to this being the beginning of a broader research program to better understand and demonstrate real world benefits of testosterone as a metabolic hormone."

In total, the 6-month, open-label MRS-TU-2019EXT study enrolled 155 men with hypogonadism, with 139 of those men included in the efficacy population. Patients were either newly recruited or previously enrolled in the MRS-TU-2019 trial. Patients began treatment at 200 mg testosterone undecanoate twice daily with meals. Doses of the therapy were titrated over 2 28-day cycles between 100 and 800 mg daily.

The primary efficacy end points were the percentage of patients with a mean plasma total testosterone concentration over 24 hours within the normal range of 222 ng/dL to 800 ng/dL on the final pharmacokinetic visit at day 90 of the study, as well as the change from baseline in the 24-hour mean SBP, as measured by ambulatory blood pressure monitoring after 120 days of treatment. Safety end points included the incidence of AEs, serious AEs, and AEs leading to study withdrawal during treatment.

Based on data from the MRS-TU-2019EXT study, testosterone undecanoate received FDA approval in August 2022 for the treatment of men with hypogonadism.³

"The world is experiencing a crisis related to men's health, and we firmly believe that oral testosterone in the form of KYZATREX has the potential to be a critical part of the solution," said Shalin Shah, CEO of Marius Pharmaceuticals, in the news release.² "Not only does the data demonstrate that KYZATREX is a safe and effective form of testosterone replacement therapy, but it also shows that KYZATREX is effective at decreasing the amount of sex hormone binding globulin (SHBG) and increasing the amount of free testosterone in the body. We believe combining the convenience of our oral delivery system with the testosterone-boosting benefits of testosterone undecanoate can be transformative for men suffering from testosterone deficiency and in helping to correct the substantial drop in testosterone levels among men in the United States over the past few decades."

References

1. Bernstein JS, Dhingra OP. A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Ther Adv Urol. 2024 Apr 10:16:17562872241241864. doi:10.1177/17562872241241864

2. Marius Pharmaceuticals announces final published phase 3 data from MRS-TU-2019EXT studying the safety and efficacy of FDA-approved KYZATREX (testosterone undecanoate) CIII capsules. News release. Marius Pharmaceuticals. April 11, 2024. Accessed April 12, 2024. https://www.prnewswire.com/news-releases/marius-pharmaceuticals-announces-final-published-phase-3-data-from-mrs-tu-2019ext-studying-the-safety-and-efficacy-of-fda-approved-kyzatrex-testosterone-undecanoate-cii-capsules-302114685.html

3. Marius Pharmaceuticals receives FDA approval of KYZATREX, an oral testosterone replacement therapy. News release. Marius Pharmaceuticals. August 2, 2022. Accessed April 12, 2024. https://www.biospace.com/article/releases/marius-pharmaceuticals-receives-fda-approval-of-kyzatrex-an-oral-testosterone-replacement-therapy/