Marius Pharmaceuticals Helps Drive FDA’s Landmark Testosterone Label Update, Removing Black Box Warning

/EIN News/ -- RALEIGH, N.C., March 03, 2025 (GLOBE NEWSWIRE) -- Marius Pharmaceuticals, is pleased to announce that the U.S. Food and Drug Administration (FDA) has implemented significant labeling changes for KYZATREX® (testosterone undecanoate) CIII capsules. This decision follows the conclusion of the TRAVERSE trial and comprehensive blood pressure monitoring studies, marking a pivotal advancement in testosterone replacement therapy (TRT).

In September 2024, Marius Pharmaceuticals proactively submitted a Prior Approval Supplement (PAS) to the FDA, advocating for the removal of the Black Box Warning associated with testosterone products. Based on the overwhelming large body of evidence through the last decade, this filing was driven by a commitment to ensuring that patients have access to safe and effective therapies without unwarranted concerns.

The TRAVERSE trial, a large-scale clinical study with over 5,000 patients, published in 2023, concluded that TRT does not increase the risk of adverse cardiovascular outcomes in men with hypogonadism. As a result, the FDA has officially removed the previous Boxed Warning related to cardiovascular risks from all testosterone product labels.

Since the initial concerns about cardiovascular (CV) risk led to label changes in 2014, extensive research has reaffirmed the safety and benefits of testosterone therapy. A global consensus has emerged on testosterone’s cardiovascular profile, supported by robust studies. Notably, an 83,000-patient study from the Veterans Affairs (VA) system concluded that men receiving TRT experienced cardiovascular benefits.¹

The strength of these studies, combined with today’s FDA decision, shifts the conversation from "Is testosterone safe?" to "What are the full health benefits testosterone can provide?"

“The removal of the box warning and long anticipated scientific conclusion opens up access to tens of millions of patients globally that can benefit from adequate testosterone therapy,” said Himanshu H. Shah, Executive Chairman of Marius.

The FDA now requires that all testosterone products include product-specific information regarding potential increases in blood pressure. Warnings about elevated blood pressure will be added to products such as testosterone injections and gels, which previously lacked such information, ensuring comprehensive patient awareness.

“For years, patients have been unduly apprehensive about testosterone replacement therapy due to the Black Box Warning, leading many to avoid a treatment that could significantly improve their health,” said Shalin Shah, CEO of Marius. “With the removal of this warning, patients and providers can finally have an informed, evidence-based discussion about the true benefits and risks of TRT. This positive shift will also accelerate Marius Pharmaceuticals’ research into additional therapeutic uses of testosterone.”

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). 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. Sharma, Rishi et al. “Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.” European heart journal vol. 36,40 (2015): 2706-15. doi:10.1093/eurheartj/ehv346
   

Media Contact:
Lilly Washburn
lilly@mariuspharma.com