FDA grants tentative approval to oral testosterone for men with hypogonadism
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The FDA granted tentative approval to oral testosterone for testosterone replacement therapy in men with conditions associated with a deficiency or absence of endogenous testosterone, according to an industry press release.
Oral testosterone (Tlando, Lipocine) has met all required quality, safety and efficacy standards necessary for approval, according to the company; however, the drug is not eligible for final approval and marketing in the U.S. until the expiration of the exclusivity period previously granted to Clarus Therapeutics for oral testosterone undecanoate (Jatenzo), which expires March 27, 2022.
As Healio previously reported, the FDA approved Clarus Therapeutics’ testosterone capsule to treat men with certain forms of hypogonadism, in March 2019. That approval marked the first new oral testosterone replacement product in more than 60 years.
The FDA issued a complete response letter for Tlando in November 2019. At the time, the complete response letter identified one deficiency, stating the efficacy trial did not meet the three secondary endpoints for maximal testosterone concentrations, according to Lipocine. The letter did not identify specific issues relating to the chemistry, manufacturing or controls of the drug.
In the release announcing the tentative approval, Lipocine said it is reviewing FDA’s tentative approval and “remains committed to taking appropriate actions with the goal of receiving final approval to permit the launch of Tlando.”
The FDA also required Lipocine to conduct certain postmarketing studies to assess patient understanding of key risks related to oral testosterone and evaluate development of adrenal insufficiency with chronic oral testosterone therapy.
“We are pleased to have received this tentative approval for Tlando,” Mahesh Patel, chairman, president and CEO of Lipocine, said in the release. “The tentative approval is supported by a strong clinical and [chemistry, manufacturing and control] data package. This is an important step towards getting our oral testosterone replacement therapy no-titration option to patients. We are committed to working towards obtaining final approval of Tlando.”
Patel said the company believes that the therapy “represents a differentiated testosterone replacement therapy for treating hypogonadism in men, with the potential to both improve patient compliance and overcome inadvertent testosterone transference and pulmonary oil microembolism risks, effects often associated with existing nonoral treatments.”
Perspective
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The tentative approval of a new oral testosterone product (Tlando) is a welcome addition to the treatment armamentarium for health care providers offering testosterone therapy to men with testosterone deficiency. Numerous formulations are already approved, yet none appears perfect, hence the continued search for the magic bullet. Topicals have variable absorption and a black box warning regarding skin-to-skin transference. Injections — either intramuscular or subcutaneous — and subcutaneous pellets seem too invasive for some patients. A nasal gel has fairly short intervals of normalized testosterone levels over 24 hours. While all of these can be effective, the holy grail in the field has been the development of a pill that does not cause severe liver toxicity, such as the alkylated testosterone that is avoided by health care providers.
One such pill has already been approved, Jatenzo by Clarus, and now Tlando by Lipocine. Both formulations avoid first-pass hepatic metabolism by their highly liphophilic design, causing them to be absorbed further downstream via gut lymphatics. Jatenzo has an adjustable dosage schedule based on blood test results and symptom relief, whereas Tlando has a single dose, which Lipocene claims reduces the need for follow-up testing and dose adjustment. This remains to be seen in clinical practice, where raising testosterone levels into the lower end of the “normal range” may not provide as much symptomatic benefit as values in the upper half of normal. Clinical experience with the previously approved Jatenzo has been relatively limited to date due to insurance challenges and then COVID-19. While an oral formulation sounds great, only time will tell how these medications are used in clinical practice.
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