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

RALEIGH, NC (April 11, 2024) — Marius Pharmaceuticals, a pharmaceutical company focused on developing innovative therapies for testosterone deficiency, today announced published results from MRS-TU-2019EXT, a six-month clinical trial of 139 men with low testosterone studying the safety and efficacy of its oral testosterone replacement therapy, KYZATREX® (testosterone undecanoate) CIII Capsules in adult men with conditions associated with a deficiency or absence of endogenous testosterone. The data, published in Therapeutic Advances in Urology, demonstrated that KYZATREX was up to 96% effective at Day 90 at restoring normal testosterone levels in adult men who have low or no testosterone levels due to certain medical conditions.1*

*Per label, 88% of patients had low testosterone levels at Day 90 (worst-case scenario calculation, excluding Site 104). Based on patients who completed the study (n=127), 96% of patients achieved normal testosterone levels at Day 90.1

“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, chief executive officer of Marius Pharmaceuticals. “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.”

Select Results from MRS-TU-2019EXT

MRS-TU-2019EXT was a 6-month, open-label study involving 139 hypogonadal men (median age of 50 years; range 22 to 66 years). The primary efficacy endpoint was the percentage of KYZATREX-treated patients with mean plasma total testosterone concentration (Cavg) over 24-hours within the normal range of 222-800 ng/dL on the final pharmacokinetic visit of the study at Day 90. KYZATREX demonstrated the following:

Up to 96 Efficacy1
Per label, 88% of patients had low testosterone levels at Day 90 (worst-case scenario calculation, excluding Site 104). Based on patients who completed the study (n=127), 96% of patients achieved normal testosterone levels at Day 90.
Safety Profile
- After 120 days of treatment, the change in 24-hour mean systolic blood pressure from baseline was 1.7 mmHg (95% CI, 0.3 to 3.1). After 190 days of treatment the blood pressure change appeared stable with a mean increase of 1.8 mmHg (95% CI, 0.3 to 3.2).1
- Only one drug-related adverse event was observed in more than 2% of study participants: hypertension (2%).1
- The article notes that, “The reported mean increase in systolic BP (blood pressure) is the lowest of the label-reported BP increases for the three FDA-approved oral TU (testosterone undecanoate) products.”1
2x Increase in Free Testosterone1
Mean Free Testosterone levels increased from 7.0 ng/dL to 14.1 ng/dL after 90 days of treatment.
Impact on FSH and LH
While both FSH (follicle stimulating hormone) and LH (luteinizing hormone), which are critical for sperm production and male fertility, both decreased after 90 and 180 days of KYZATREX treatment, levels did not drop to zero at either of the two post-Baseline visits.1

The authors of the study were James S. Bernstein, PhD, and Om Dhingra, PhD, board director and scientific advisor to Marius Pharmaceuticals.

Om Dhingra commented, “The excellent safety and efficacy data can be attributable to KYZATREX’s innovative and elegant formulation. 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 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.”

Testosterone deficiency – or hypogonadism – is a chronic disease that affects about 30 percent of men aged 20 years and older.2 In a 24-year study, researchers noted a substantial age-independent decline in testosterone levels among men in the U.S. Since the study’s inception in 1984, it was determined that men born in more recent years have lower testosterone levels than previous generations, with average levels declining by about 1% per year.3 Compounding the issue, it’s been reported that only 5-10% of men with low testosterone are being treated with testosterone replacement therapy (TRT).4

Historically, TRT has been administered through injections, pellets and gels. KYZATREX is designed to utilize lymphatic absorption to bypass first-pass metabolism to drive uptake and prevent liver damage. KYZATREX is an immediate-release formulation with twice-daily dosing that, when administered every 12 hours, closely mimics the diurnal rhythm of endogenous testosterone, as demonstrated by the pharmacokinetic data in the study article.1