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

Data Published in Therapeutic Advances in Urology Demonstrates Up to 96% Efficacy in Helping Restore Testosterone Levels to Normal at Day 90^1*

RALEIGH, N.C., April 11, 2024 /PRNewswire/ -- 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

This published study is part of Marius Pharmaceuticals' comprehensive effort to develop innovative therapies for testosterone deficiency. To learn more about KYZATREX^®, visit https://www.kyzatrex.com. To learn more about Marius Pharmaceuticals, visit https://www.mariuspharma.com.

The full journal article can be found here.

About KYZATREX^® (testosterone undecanoate)
KYZATREX is a proprietary softgel oral formulation absorbed primarily via the lymphatic system (meaning it is not toxic to the liver) indicated in adult males for conditions associated with a deficiency or absence of endogenous testosterone. The safety and efficacy of KYZATREX was demonstrated in a phase 3, multi-center, open-label, six-month study in 155 hypogonadal males between 18 and 65 years of age with documented hypogonadism, as defined by a below normal serum testosterone level (≤281 ng/dL) and at least one sign or symptom of testosterone deficiency. In the efficacy population (n=139), 88 percent of hypogonadal men treated with KYZATREX achieved a mean plasma total testosterone concentration (Cavg) over 24 hours within the normal range (222-800 ng/dL) on the final pharmacokinetic (PK) visit of the study at Day 90 (primary endpoint). Based on exploratory endpoints, patients who received KYZATREX reported improvements in quality of life, energy/fatigue, erectile function, intercourse satisfaction, and positive mood. The most common side effect reported in ≥2 percent of KYZATREX patients was increased blood pressure (2.6%). The safety and efficacy of KYZATREX in males less than 18 years old have not been established.

Please see additional Important Safety Information below, including Boxed Warning for potential increased blood pressure, for KYZATREX or visit www.kyzatrex.com.

About Marius Pharmaceuticals
Marius Pharmaceuticals strives to better the lives of men and women by focusing on therapies designed for hypogonadism or Testosterone Deficiency. Their vision is to holistically improve metabolic health and mitigate significant unnecessary costs to the global healthcare system. For more information, please visit www.mariuspharma.com.

Important Safety Information for KYZATREX^® (testosterone undecanoate)

Use
KYZATREX (testosterone undecanoate) is a prescription drug that is used to treat adult men who have low or no testosterone levels due to certain medical conditions. KYZATREX is a controlled substance (CIII) because it contains testosterone. It is not known if KYZATREX is safe or effective in males younger than 18 years old. Improper use may affect bone growth in children. KYZATREX is not meant for use by women.

Important Safety Information for KYZATREX^® (testosterone undecanoate)

KYZATREX can increase blood pressure, which can increase the risk of having a heart attack or stroke and can increase risk of death due to a heart attack or stroke. Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke.

• If your blood pressure increases while on KYZATREX, blood pressure medicines may need to be started. If you are currently taking blood pressure medicines, they may need to be changed or new blood pressure medicines may need to be added to control your blood pressure.
• If your blood pressure cannot be controlled, KYZATREX may need to be stopped.
• Your healthcare provider will monitor your blood pressure while you are being treated with KYZATREX.

Do not take KYZATREX if you: have breast cancer; have or might have prostate cancer; are a woman who is pregnant (KYZATREX may harm your unborn baby); are allergic to KYZATREX or any of its ingredients; or have low testosterone without certain medical conditions (e.g., do not take KYZATREX if you have low testosterone due to age).

Before you take KYZATREX, tell your healthcare provider about all of your medical conditions, including if you: have high blood pressure or are treated for high blood pressure; have a history of diabetes; have heart problems; have high red blood cell count (hematocrit) or high hemoglobin laboratory value; have urinary problems due to an enlarged prostate; have liver or kidney problems; or have problems breathing while you sleep (sleep apnea).

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking KYZATREX with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin; medicines that decrease blood clotting (blood thinners); corticosteroids; or medicines that increase blood pressure, such as some cold medicine and pain medicines.

KYZATREX may cause other serious side effects including:

• Increase in red blood cell count (hematocrit) or hemoglobin, which can increase the risk of blood clots, strokes, and heart attacks. You may need to stop KYZATREX if your red blood cell count increases.
• If you already have an enlarged prostate, your signs and symptoms may worsen while taking KYZATREX. These may include: increased urination at night; trouble starting your urine stream; urinating many times during the day; urge to go to the bathroom right away; a urine accident; inability to pass urine or weak urine flow.
• Increased risk of prostate cancer.
• Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.
• Abuse. Testosterone can be abused when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious heart and psychological side effects.
• In large doses, KYZATREX may lower your sperm count.
• Liver problems. Symptoms of liver problems may include: nausea or vomiting; yellowing of your skin or whites of your eyes; dark urine; pain on the right side of your stomach area (abdominal pain).
• Swelling of your ankles, feet, or body (edema), with or without heart failure.
• Enlarged or painful breasts.
• Breathing problems while you sleep (sleep apnea).

Call your healthcare provider right away if you have any of the serious side effects listed above.

The most common side effect of KYZATREX is high blood pressure. Other side effects may include headache, joint or back pain, diarrhea, increased red blood cell count, anxiety, constipation, swelling of the legs, and increased prostate specific antigen (PSA) levels.
These are not all the possible side effects of KYZATREX. For more information, ask your healthcare provider or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Marius by calling 1-833-949-5040.

Keep KYZATREX and all medicines out of the reach of children.

See Full Prescribing Information and Medication Guide for KYZATREX.

References:

1. Bernstein JS, Dhingra O. "A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product." Ther Adv Urol. 2024;16:1-17. 2024; doi:10.1177/17562872241241864
    
2. Peterson MD, Belakovskiy A, McGrath R, Yarrow JF. Testosterone deficiency, weakness, and multimorbidity in men. Sci Rep. 2018;8(1):5897. doi:10.1038/s41598-018-24347-6
    
3. Thomas G. Travison TG, Araujo AB, O'Donnell AB, et al., Andre B. Araujo, Amy B. O'Donnell, Varant Kupelian, John B. McKinlay, A Population-Level Decline in Serum Testosterone Levels in American Men, J Clin Endocrinol Metab. January 2007, 92(1):196-202
    
4. Krakowsky Y, Grober E. Testosterone deficiency – Establishing a Biochemical Diagnosis. EJIFCC. 2015 Mar; 26(2): 105–113.PMID: 27683486; PMCID: PMC4975356. Accessed 9 Feb. 2024.

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SOURCE Marius Pharmaceuticals