ReTune Study

/ hīpō • Gōna • dizəm /

Commonly referred to “Low Testosterone” or “Testosterone Deficiency”, this disease has a profound impact on the lives of men of all ages who present symptoms such erectile dysfunction, depression, fatigue, anemia, increased body fat and more. Male hypogonadism affects 15 million in the US alone.

At Marius, we continue to research and investigate the vital role testosterone plays in all of these functions and more in order to make sure those afflicted can live their best possible lives.

The ReTUne Study is our pivotal Phase 3 study with a main study and extension study measuring the efficacy and safety of our proprietary Oral Testosterone for primary and secondary hypogonadism in males aged 18-65. From a design perspective, one of the most comprehensive trials to date, we tested 295 patients across 6 and 12 month studies and some patients had a total of 18 months of exposure to the drug. We have tested for exploratory endpoints including Patient Reported Outcomes and other important biomarkers. This study was successfully completed in 2019.

The proposed indications for Kyzatrex demonstrated through the study are:

  • Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.

  • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range.

Comorbidity Rate with Testosterone Deficiency

Muscle Mass Frailty NASH / NAFLD Obesity Diabetes Fatigue Sex Drive Sleep Apnea Depression
>$75BN Pharma Spend
Cardiovascular/Metabolic
Obesity 52.4%
Diabetes 50%
NASH/NAFLD 49.1%
Hypertension 42.4%
Hyperilpidemia 40.4%
>$9BN Pharma Spend
Musculoskeletal/Bone
Osteoporosis 44.4% †
>$5.5BN Pharma Spend
Urological
Erectile Dysfunction 40% †
Source: IQVIA, Symphony Health
† = Key Addressable Areas of Marius Clinical Development Currently

Formulation Innovation

Marius innovative formulation utilized lymphatic absorption to by-pass the first pass metabolism of the liver and drive better uptake rates. Our innovative formulation also utilizes phytosterols, which are GRAS excipients, however being used for the first time in a RX product to help drive absorption profiles and potentially improved clinical results.

Lymphatic Absorption

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Important Industry Papers

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

"Nine resolutions were debated amongst an international expert consensus conference, with unanimous approval (including) 1. TD (Testosterone Deficiency) is a well-established, clinically significant medical condition that negatively affects male sexuality, reproduction, general health and quality of life 2. the evidence does not support increased risks of cardiovascular events with T therapy, 3. The evidence supports a major research initiative to explore the benefits of T therapy for cardiometobolic disease including diabetes."

Remission of Type 2 Diabetes following Long Term TRT Treatment

"Long-term TTh in men with T2DM and hypogonadism improves glycemic control and insulin resistance. Remission of diabetes occurred in one-third of the patients. TTh is potentially a novel additional therapy for men with T2DM and hypogonadism."

Testosterone and Cardiovascular Health

"Normal physiologic levels of testosterone are beneficial to the male cardiovascular (CV) system, and testosterone deficiency is associated with an unfavorable metabolic profile and increased CV disease states."

Overselling Hysteria – Correcting Controversies in Testosterone

"More than 100 other studies have shown no increased CV risk, or even reduced risk, among men with higher endogenous testosterone concentrations or who received testosterone therapy. High-level evidence demonstrates an inverse relationship for serum testosterone and mortality, incident coronary artery disease, severity of coronary artery disease, atherosclerosis, and carotid intima-media thickness."