Meeting News

New testosterone therapies offer options for men with hypogonadism

NEW ORLEANS — Three new testosterone therapies offer innovative drug delivery options for men with hypogonadism that improve patient satisfaction while avoiding risks related to secondary exposure, according to several speakers at the Androgen Society annual meeting.

Speaking during a session on new and emerging testosterone therapies, the presenters noted that newer testosterone preparations offer men with hypogonadism discrete, easier-to-use options that can restore physiologic testosterone levels and improve sexual function. One such option, oral testosterone undecanoate (Jatenzo, Clarus Therapeutics), was approved by the FDA 5 days after the presentation.

“It is amazing to see three completely different, unique applications — you have a nasal, you have an injectable and an oral,” said Mohit Khera, MD, MBA, MPH, professor of urology and director of the Laboratory for Andrology Research at McNair Medical Institute, Baylor College of Medicine in Houston, who moderated the session.

Oral testosterone undecanoate A new oral testosterone therapy offers men with certain forms of hypogonadism a novel formulation that reduces the dietary-fat effect and variability of testosterone response observed with previous oral formulations, according to a speaker.

Ronald Swerdloff

Oral testosterone undecanoate, approved by the FDA on March 27, is the first new oral testosterone replacement product in more than 60 years, 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, said during a presentation. The drug is indicated for men with low testosterone levels due to specific medical conditions, such as Klinefelter syndrome or tumors that have damaged the pituitary gland.

In an interview before the drug’s approval was announced, Swerdloff said the agent has “excellent pharmacokinetics” and, when taken with meals, has few unanticipated adverse effects.

“The development of Jatenzo has been complex due to challenges associated with the oral dosing of testosterone undecanoate,” Swerdloff said during a presentation. “However, the Jatenzo formulation reduces the dietary fat effect and the variability of testosterone response that we have seen previously with Andriol.”

In addition, the post-collection conversion of testosterone undecanoate to testosterone must be accounted for in clinical trials of oral testosterone undecanoate formulations, Swerdloff said, to accurately establish efficacy. In developing oral testosterone undecanoate, researchers derived a conversion factor to enable the use of serum to assess testosterone response to the drug and direct dose-titration in a clinical setting, he said.

Oral testosterone undecanoate contains a boxed warning on its label stating that the drug can cause hypertension, increasing cardiovascular 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 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.

Swerdloff called the agent a “long-awaited option for physicians and their hypogonadal male patients.”

“This is quite innovative and I think it will have an impact once it gets to the marketplace,” Swerdloff said.

Testosterone enanthate injection A once-weekly, single-use autoinjector of testosterone enanthate for men with primary or hypogonadotropic hypogonadism can provide physiologically normal testosterone levels with minimal peaks and troughs for as long as a patient continues with the therapy, according to a speaker.

The testosterone enanthate injection (Xyosted, Antares Pharma Inc.), approved by the FDA in October, is available in 50-mg, 75-mg and 100-mg doses in a single-use, disposable QuickShot injection device for use at home.

Jed Kaminetsky

“The take-home messages are this therapy provides consistent, stable testosterone levels, easy, painless injections and very high patient satisfaction without the mess of gels or the pain of pellets,” Jed Kaminetsky, MD, clinical assistant professor in the department of urology at New York University Langone Health, and medical director of Manhattan Medical Research, told Endocrine Today. “Most surprising is the pharmacokinetic data — a peak/trough ratio of 1.8.”

Kaminetsky said the subcutaneous dosing of testosterone enanthate also removes transfer concerns commonly associated with gels and potentially reduces the need for in-office injection procedures that may require more frequent patient visits.

Data from a 52-week, phase 3 study evaluating the efficacy and safety of testosterone enanthate in 150 men with a documented diagnosis of hypogonadism (mean age, 53 years) demonstrated that the treatment was generally well-tolerated, Kaminetsky said. The most commonly observed adverse effects were an increase in hematocrit (mean, 5.4% at 52 weeks) and hypertension; however, Kaminetsky said patients with hypertension at baseline appeared to experience less impact on BP after initiating treatment. Additionally, patients using antihypertensive medications experienced BP changes comparable to those not assigned to testosterone enanthate, and researchers did not observe a “clear relationship” between total testosterone levels and BP, he said.

No adverse CV events were reported during the study.

Testosterone enanthate has a boxed warning alerting patients and prescribers to possible increases in BP that can lead to CV events.

Testosterone nasal gel The first approved intranasal testosterone gel offers men with hypogonadism a unique formulation that promises rapid absorption and onset of action with lower adverse effects, according to a speaker.

Testosterone nasal gel (Natesto, Aytu BioScience) was approved by the FDA in 2014 for use in men with primary or hypogonadotropic hypogonadism, congenital or acquired, and is self-administered via a nasal applicator, minimizing the risks of secondary exposure to testosterone by women or children.

“You have a very high vasculature in the nasal mucosa, so you are able to have this rapid absorption, directly into the bloodstream and avoid first-pass metabolism.” Gerwin Westfield, PhD, director of medical affairs at Aytu BioScience in Columbus, Ohio, said during a presentation. The therapy is low-volume, needle-free and user-friendly and features an innovative thixotropic gel that is self-adhesive, he said, so the patient avoids a “drip” out of the nose.

The pharmacokinetic profile of testosterone nasal gel is unique, Westfield said. The maximum concentration of testosterone is reached about 45 minutes after administration, and there is quick clearance 2 to 6 hours after administration, he said. Available as a metered-dose pump, one pump delivers 5.5 mg testosterone. The recommended dose is 11 mg — one pump per nostril — applied three times daily, for a total of 33 mg each day.

“Among patients dosed three times daily, 90% of those men were deemed to be in the eugonadal range,” Westfield said. “When you talk about symptomatic improvement, in all five domains of erectile dysfunction, there was improvement within 30 days, and this improvement continued throughout the 90-day treatment period.”

The drug is contraindicated in men with breast cancer or known or suspected prostate cancer, and not recommended for use in patients with chronic nasal conditions. – by Regina Schaffer

Reference:

Swerdloff R, et al. New and emerging therapies. Presented at: The Androgen Society 2nd Annual Meeting; March 21-22, 2019; New Orleans.

Disclosures: Kaminetsky reports he has served as a consultant for Antares Pharma Inc., Endo Pharmaceuticals and Marius Pharmaceuticals and has served as a research investigator for Clarus Therapeutics and Lipocine Inc. Swerdloff reports he is a consultant for Clarus Therapeutics and was a principal investigator for several clinical studies conducted by Clarus Therapeutics. Westfield reports he is medical affairs manager of Aytu BioScience Inc.

NEW ORLEANS — Three new testosterone therapies offer innovative drug delivery options for men with hypogonadism that improve patient satisfaction while avoiding risks related to secondary exposure, according to several speakers at the Androgen Society annual meeting.

Speaking during a session on new and emerging testosterone therapies, the presenters noted that newer testosterone preparations offer men with hypogonadism discrete, easier-to-use options that can restore physiologic testosterone levels and improve sexual function. One such option, oral testosterone undecanoate (Jatenzo, Clarus Therapeutics), was approved by the FDA 5 days after the presentation.

“It is amazing to see three completely different, unique applications — you have a nasal, you have an injectable and an oral,” said Mohit Khera, MD, MBA, MPH, professor of urology and director of the Laboratory for Andrology Research at McNair Medical Institute, Baylor College of Medicine in Houston, who moderated the session.

Oral testosterone undecanoate A new oral testosterone therapy offers men with certain forms of hypogonadism a novel formulation that reduces the dietary-fat effect and variability of testosterone response observed with previous oral formulations, according to a speaker.

Ronald Swerdloff

Oral testosterone undecanoate, approved by the FDA on March 27, is the first new oral testosterone replacement product in more than 60 years, 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, said during a presentation. The drug is indicated for men with low testosterone levels due to specific medical conditions, such as Klinefelter syndrome or tumors that have damaged the pituitary gland.

In an interview before the drug’s approval was announced, Swerdloff said the agent has “excellent pharmacokinetics” and, when taken with meals, has few unanticipated adverse effects.

“The development of Jatenzo has been complex due to challenges associated with the oral dosing of testosterone undecanoate,” Swerdloff said during a presentation. “However, the Jatenzo formulation reduces the dietary fat effect and the variability of testosterone response that we have seen previously with Andriol.”

In addition, the post-collection conversion of testosterone undecanoate to testosterone must be accounted for in clinical trials of oral testosterone undecanoate formulations, Swerdloff said, to accurately establish efficacy. In developing oral testosterone undecanoate, researchers derived a conversion factor to enable the use of serum to assess testosterone response to the drug and direct dose-titration in a clinical setting, he said.

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Oral testosterone undecanoate contains a boxed warning on its label stating that the drug can cause hypertension, increasing cardiovascular 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 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.

Swerdloff called the agent a “long-awaited option for physicians and their hypogonadal male patients.”

“This is quite innovative and I think it will have an impact once it gets to the marketplace,” Swerdloff said.

Testosterone enanthate injection A once-weekly, single-use autoinjector of testosterone enanthate for men with primary or hypogonadotropic hypogonadism can provide physiologically normal testosterone levels with minimal peaks and troughs for as long as a patient continues with the therapy, according to a speaker.

The testosterone enanthate injection (Xyosted, Antares Pharma Inc.), approved by the FDA in October, is available in 50-mg, 75-mg and 100-mg doses in a single-use, disposable QuickShot injection device for use at home.

Jed Kaminetsky

“The take-home messages are this therapy provides consistent, stable testosterone levels, easy, painless injections and very high patient satisfaction without the mess of gels or the pain of pellets,” Jed Kaminetsky, MD, clinical assistant professor in the department of urology at New York University Langone Health, and medical director of Manhattan Medical Research, told Endocrine Today. “Most surprising is the pharmacokinetic data — a peak/trough ratio of 1.8.”

Kaminetsky said the subcutaneous dosing of testosterone enanthate also removes transfer concerns commonly associated with gels and potentially reduces the need for in-office injection procedures that may require more frequent patient visits.

Data from a 52-week, phase 3 study evaluating the efficacy and safety of testosterone enanthate in 150 men with a documented diagnosis of hypogonadism (mean age, 53 years) demonstrated that the treatment was generally well-tolerated, Kaminetsky said. The most commonly observed adverse effects were an increase in hematocrit (mean, 5.4% at 52 weeks) and hypertension; however, Kaminetsky said patients with hypertension at baseline appeared to experience less impact on BP after initiating treatment. Additionally, patients using antihypertensive medications experienced BP changes comparable to those not assigned to testosterone enanthate, and researchers did not observe a “clear relationship” between total testosterone levels and BP, he said.

PAGE BREAK

No adverse CV events were reported during the study.

Testosterone enanthate has a boxed warning alerting patients and prescribers to possible increases in BP that can lead to CV events.

Testosterone nasal gel The first approved intranasal testosterone gel offers men with hypogonadism a unique formulation that promises rapid absorption and onset of action with lower adverse effects, according to a speaker.

Testosterone nasal gel (Natesto, Aytu BioScience) was approved by the FDA in 2014 for use in men with primary or hypogonadotropic hypogonadism, congenital or acquired, and is self-administered via a nasal applicator, minimizing the risks of secondary exposure to testosterone by women or children.

“You have a very high vasculature in the nasal mucosa, so you are able to have this rapid absorption, directly into the bloodstream and avoid first-pass metabolism.” Gerwin Westfield, PhD, director of medical affairs at Aytu BioScience in Columbus, Ohio, said during a presentation. The therapy is low-volume, needle-free and user-friendly and features an innovative thixotropic gel that is self-adhesive, he said, so the patient avoids a “drip” out of the nose.

The pharmacokinetic profile of testosterone nasal gel is unique, Westfield said. The maximum concentration of testosterone is reached about 45 minutes after administration, and there is quick clearance 2 to 6 hours after administration, he said. Available as a metered-dose pump, one pump delivers 5.5 mg testosterone. The recommended dose is 11 mg — one pump per nostril — applied three times daily, for a total of 33 mg each day.

“Among patients dosed three times daily, 90% of those men were deemed to be in the eugonadal range,” Westfield said. “When you talk about symptomatic improvement, in all five domains of erectile dysfunction, there was improvement within 30 days, and this improvement continued throughout the 90-day treatment period.”

The drug is contraindicated in men with breast cancer or known or suspected prostate cancer, and not recommended for use in patients with chronic nasal conditions. – by Regina Schaffer

Reference:

Swerdloff R, et al. New and emerging therapies. Presented at: The Androgen Society 2nd Annual Meeting; March 21-22, 2019; New Orleans.

Disclosures: Kaminetsky reports he has served as a consultant for Antares Pharma Inc., Endo Pharmaceuticals and Marius Pharmaceuticals and has served as a research investigator for Clarus Therapeutics and Lipocine Inc. Swerdloff reports he is a consultant for Clarus Therapeutics and was a principal investigator for several clinical studies conducted by Clarus Therapeutics. Westfield reports he is medical affairs manager of Aytu BioScience Inc.

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