Perspective

FDA approves oral testosterone capsule for men with hypogonadism

The FDA on Wednesday approved testosterone undecanoate in an oral capsule to treat men with certain forms of hypogonadism, the agency announced in a press release.

The approval marks the first new oral testosterone replacement product in more than 60 years. The indication is for men with low testosterone levels due to specific medical conditions, such as Klinefelter syndrome or tumors that have damaged the pituitary gland. This oral testosterone undecanoate (Jatenzo, Clarus Therapeutics) should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low testosterone, according to the FDA, which stated that the drug’s benefits do not outweigh its risks for that use.

“Jatenzo’s oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive and urologic products in the FDA’s Center for Drug Evaluation and Research, said in the release. “But it’s important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo’s effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.”

The efficacy of Jatenzo was demonstrated in a 4-month clinical trial involving 166 men with hypogonadism. Study participants initially were given Jatenzo at a dose of 237 mg twice per day, and the dose was adjusted downward or upward to a maximum of 396 mg twice per day on the basis of testosterone levels. At the end of the study, 87% of men treated with the oral testosterone undecanoate achieved an average testosterone level within the normal range, which was the primary study endpoint.

In an interview conducted before a presentation on oral testosterone undecanoate at the Androgen Society annual meeting in New Orleans this month, Ronald Swerdloff, MD, professor of medicine, endocrinology, metabolism and nutrition at the David Geffen School of Medicine at UCLA and chief of the division of endocrinology at Harbor UCLA Medical Center, told Endocrine Today that the agent has “excellent pharmacokinetics” and, when taken with meals, has few unanticipated adverse effects. Development of the drug, he said, has been complex due to challenges associated with oral dosing. The formulation of testosterone undecanoate, however, reduces a dietary fat effect and the variability of testosterone response, he said.

“We are hopeful this long sought after oral androgen will be available for treatment of hypogonadal men soon,” Swerdloff said on Friday.

Oral testosterone undecanoate contains a boxed warning on its label stating that the drug can cause hypertension, increasing CV risk. Health care providers should consider a patient’s individual CV risks and ensure that blood pressure is adequately controlled before prescribing oral testosterone undecanoate, according to the FDA; they should also periodically monitor patient BP during treatment.

Oral testosterone undecanoate is one of two testosterone products that have this boxed warning. The FDA is requiring all testosterone product manufacturers to conduct BP postmarketing trials to more clearly address whether these products increase blood pressure.

Common side effects, occurring in more than 2% of patients in the clinical trial for oral testosterone undecanoate, included headache, an increase in hematocrit, a decrease in HDL cholesterol, hypertension and nausea. An increase in prostate specific antigen (PSA) was also observed. Patients should have their hematocrit, cholesterol and PSA monitored regularly to check for changes. Those with benign prostate hyperplasia should be monitored for worsening of symptoms. – by Regina Schaffer

Disclosures: Joffe is director of the division of bone, reproductive and urologic products in the FDA’s Center for Drug Evaluation and Research. Swerdloff reports he is a consultant for Clarus Therapeutics and was a principal investigator for several clinical studies conducted by Clarus Therapeutics.

The FDA on Wednesday approved testosterone undecanoate in an oral capsule to treat men with certain forms of hypogonadism, the agency announced in a press release.

The approval marks the first new oral testosterone replacement product in more than 60 years. The indication is for men with low testosterone levels due to specific medical conditions, such as Klinefelter syndrome or tumors that have damaged the pituitary gland. This oral testosterone undecanoate (Jatenzo, Clarus Therapeutics) should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low testosterone, according to the FDA, which stated that the drug’s benefits do not outweigh its risks for that use.

“Jatenzo’s oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive and urologic products in the FDA’s Center for Drug Evaluation and Research, said in the release. “But it’s important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo’s effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.”

The efficacy of Jatenzo was demonstrated in a 4-month clinical trial involving 166 men with hypogonadism. Study participants initially were given Jatenzo at a dose of 237 mg twice per day, and the dose was adjusted downward or upward to a maximum of 396 mg twice per day on the basis of testosterone levels. At the end of the study, 87% of men treated with the oral testosterone undecanoate achieved an average testosterone level within the normal range, which was the primary study endpoint.

In an interview conducted before a presentation on oral testosterone undecanoate at the Androgen Society annual meeting in New Orleans this month, Ronald Swerdloff, MD, professor of medicine, endocrinology, metabolism and nutrition at the David Geffen School of Medicine at UCLA and chief of the division of endocrinology at Harbor UCLA Medical Center, told Endocrine Today that the agent has “excellent pharmacokinetics” and, when taken with meals, has few unanticipated adverse effects. Development of the drug, he said, has been complex due to challenges associated with oral dosing. The formulation of testosterone undecanoate, however, reduces a dietary fat effect and the variability of testosterone response, he said.

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“We are hopeful this long sought after oral androgen will be available for treatment of hypogonadal men soon,” Swerdloff said on Friday.

Oral testosterone undecanoate contains a boxed warning on its label stating that the drug can cause hypertension, increasing CV risk. Health care providers should consider a patient’s individual CV risks and ensure that blood pressure is adequately controlled before prescribing oral testosterone undecanoate, according to the FDA; they should also periodically monitor patient BP during treatment.

Oral testosterone undecanoate is one of two testosterone products that have this boxed warning. The FDA is requiring all testosterone product manufacturers to conduct BP postmarketing trials to more clearly address whether these products increase blood pressure.

Common side effects, occurring in more than 2% of patients in the clinical trial for oral testosterone undecanoate, included headache, an increase in hematocrit, a decrease in HDL cholesterol, hypertension and nausea. An increase in prostate specific antigen (PSA) was also observed. Patients should have their hematocrit, cholesterol and PSA monitored regularly to check for changes. Those with benign prostate hyperplasia should be monitored for worsening of symptoms. – by Regina Schaffer

Disclosures: Joffe is director of the division of bone, reproductive and urologic products in the FDA’s Center for Drug Evaluation and Research. Swerdloff reports he is a consultant for Clarus Therapeutics and was a principal investigator for several clinical studies conducted by Clarus Therapeutics.

    Perspective
    Abraham Morgentaler

    Abraham Morgentaler

    This is a big step forward. We have a wide range of treatments already available for men who have testosterone deficiency or hypogonadism. But, for many people, the idea of being able to take a pill — rather than a cream, a patch, an injection or a pellet — will be much more convenient and might allow to them to consider treatment when they would not have before. The concern in the past about pills is that previous formulations caused liver toxicity. This agent works differently. It is absorbed through the lymphatic system, rather than the bloodstream, and therefore bypasses metabolism by the liver, the so-called “first-pass effect.”

    Important to realize is that the treatment is likely to be useful to many men, though it remains unclear how it is going to fit into our choices of treatment. We have yet to see how this works out in regular medical practice. For some men, how well the testosterone levels are sustained may make the difference. Also, a lot of people don’t take their pills, especially when the dose is more than once per day. But, on the whole, this is a very positive outcome.

    • Abraham Morgentaler, MD
    • Director, Men’s Health, Boston
      Associate Clinical Professor of Surgery
      Beth Israel Deaconess Medical Center, Harvard Medical School

    Disclosures: Morgentaler reports he has received payments from Acerus and Aytu BioScience.