Marius Pharmaceuticals, which helped secure FDA removal of Black Box Warning, says regulatory shift marks a milestone for patient access and treatment options.
By AB Wire
The U.S. Food and Drug Administration (FDA), on February 28, removed the Black Box Warning on testosterone replacement therapy (TRT) products. This regulatory change follows extensive clinical research, including the TRAVERSE trial, which demonstrated no increased cardiovascular risk associated with TRT.
Among the drugs whose Black Box Warning is removed is Kyzatrex, an FDA-approved treatment for testosterone deficiency developed by the Raleigh, N.C., -based Marius Pharmaceuticals.
Marius, which helped drive the landmark label update, welcomed the move saying the regulatory shift marks a milestone for patient access and treatment options.
A Black Box Warning is the most serious warning issued by the FDA for prescription drugs. It appears on a drug’s label to alert healthcare providers and patients about significant risks, such as severe or life-threatening side effects. These warnings are placed to signal that a medication could cause serious harm. The removal of a Black Box Warning, as seen in the case of testosterone replacement therapy, typically indicates that new evidence has demonstrated the risks are lower than previously thought.
“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 in a press release.
The move is a major victory for patients and healthcare providers who have long sought clarity on the safety of testosterone therapy, the release noted. Since the initial cardiovascular risk warning was added to TRT labels in 2014, accumulating evidence has pointed to the therapy’s benefits rather than harm. A significant study from the Veterans Affairs (VA) system, encompassing over 83,000 patients, even suggested cardiovascular benefits for men undergoing TRT.
READ: Fixing metabolic health through hormones: Marius CEO on Kyzatrex and testosterone deficiency (February 21, 2025)
“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.”
Marius played a pivotal role in advocating for the label update. The company submitted a Prior Approval Supplement (PAS) to the FDA in September 2024, arguing that the scientific consensus overwhelmingly supported the safety of TRT.
While the FDA has removed the cardiovascular risk warning, it now requires all testosterone products to carry label information about potential increases in blood pressure. This adjustment ensures that patients remain informed about all aspects of treatment, particularly with formulations like injections and gels that previously lacked such details.
READ: Testosterone doses help men ward off heart disease, prolong life: study by cardiologist Dr. Rajat Barua (August 11, 2015)
With the regulatory hurdle cleared, Marius said the company plans to expand its research into the broader therapeutic applications of testosterone.
The FDA’s decision reflects a growing global consensus on TRT’s safety and effectiveness. As research continues, healthcare providers can now engage in more evidence-based discussions with patients, ensuring informed choices about testosterone therapy’s role in their overall health and well-being.
In a recent interview with The American Bazaar, Marius CEO Shah noted that testosterone is a critical marker of overall health, yet it remains widely misunderstood. “Testosterone therapy has been used successfully for nearly a century — including for women during menopause — but its progress was hindered in the 1990s when it was classified as a Schedule III controlled substance,” he said. “Despite opposition from the FDA, the AMA, and the DEA, this decision was driven by political pressure rather than science.”
An estimated 20 million men between ages 25 and 75 in the U.S. suffer from low testosterone. Despite its high prevalence, hypogonadism often goes undiagnosed and untreated, leading to downstream health consequences such as metabolic disorders, cardiovascular disease, and reduced quality of life, Shah said, adding that addressing this condition is crucial for improving overall health outcomes and preventing chronic disease.
Testosterone plays a vital role in both metabolic and cardiovascular health, he pointed out. “It acts as an insulin sensitizer, helping to improve glucose metabolism and potentially benefiting men with Type 2 diabetes,” he said. “Research has shown that testosterone therapy can slow or even reverse atherosclerosis, lower cholesterol levels, and reduce the risk of heart disease in aging men.”